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Renal cell carcinoma (RCC) is a common malig- nancy of the urinary system. Although traditional therapies, such as surgery assisted with chemotherapy have improved the quality of life and survival time of patients with RCC, patients with metastasis or recurrence benefit little from such therapies. At present, little is known about the underlying mechanisms of RCC, rendering treatment selection and implementation challenging. Therefore, investigating the cause and underlying mechanisms of RCC remain of importance to explore poten- tial new avenues for its treatment. Inter-α-trypsin inhibitor heavy chain 1 (ITIH1) is an inflammation-associated gene reported to suppress the progression of liver cancer. However, its role in RCC remains poorly understood. Therefore, the present study aimed to investigate the role and mechanism of ITIH1 in RCC. Based on data obtained from The Cancer Genome Atlas database, ITIH1 expression was demonstrated to be significantly higher in tumor tissues compared with normal tissues, which was in turn negatively associated with the survival of patients with RCC. However, in RCC cells, ITIH1 was shown to be expressed at significantly lower levels compared with those in HK-2 cells. The discrepancy between tissues and cell lines might be due to the different environment of cell growth. ITIH1 knockdown in RCC cells significantly increased cell proliferation and invasion whilst significantly decreasing the apoptosis rate, compared with those in control cells (without ITIH1 knockdown). By contrast, overexpression of ITIH1 significantly inhibited cell proliferation and inva- sion in RCC cells. In terms of western blotting results, the phosphorylation levels of NF-κB were significantly increased following ITIH1 knockdown. The protein expression level of IκB significantly decreased whereas that of IKK, Cyclin D1, proliferating cell nuclear antigen and α-smooth muscle actin were significantly increased in ITIH1-knockdown cells, compared with those in the control cells (without ITIH1 knockdown). This suggests that the NF-κB pathway may be activated after ITIH1 knockdown. Following treatment with the NF-κB pathway inhibitor JSH-23 in combination with ITIH1 knockdown, RCC cell proliferation and invasion were significantly reduced compared with those after ITIH1 knockdown alone. In summary, results from the present study suggest that ITIH1 can serve an inhibitory role in the progres- sion of RCC, which could potentially be inhibited through the NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a highly lethal disease, and surgical resection is one of the major treatment methods used. However, to date, at least to the best of our knowledge, there is no effective prognostic scoring system for the overall survival (OS) and relapse-free survival (RFS) of patients following hepatectomy. The present study developed a low-cost and easy-to-use model based on the clinicopathological characteristics of patients with HCC for assessment of outcome prediction and risk stratification. A total of 690 patients with HCC undergoing surgery were included and randomly divided into two cohorts (n=345). Cox regression analysis was conducted to investigate the association between the clinicopathological and treatment features, and patient survival. Multivariate analysis revealed that ascites, vascular tumor thrombus, low tumor differentiation and extrahepatic metastasis were independent risk factors for OS. Extrahepatic metastasis and multiple tumors were independent risk factors to predict tumor recurrence. These variables were weighted to construct the ascites, vascular tumor thrombus, low tumor differentiation, extrahepatic metastasis and multiple tumors (AVLEM) score based on the cumulative incidence (CuI) of the aforementioned variables, and the patients were classified into grade 0 (CuI=0), grade 1 (CuI=1 for OS and CuI ≥1 for RFS), and grade 2 (CuI ≥2) subgroups, respectively. Kaplan-Meier analysis revealed that the OS and RFS differed significantly among the subgroups; however, the survival rate between the two cohorts did not exhibit any marked differences. On the whole, the present study demonstrates that with this AVLEM scoring system, patients with HCC with a high score had a poor OS and RFS; thus, it is suggested that such patients undergo imaging examinations following a hepatectomy more frequently. [ABSTRACT FROM AUTHOR]

The prognostic impact of baseline C-reactive protein (CRP) in patients with cancer receiving immune checkpoint inhibitors (ICIs) is unclear. The present meta-analysis aimed to review the prognostic value of baseline C-reactive protein (CRP) levels for patients with cancer receiving immunotherapy. Electronic databases, including PubMed, EMbase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, WanFang, Chinese Literature Biomedical Database and Weipu Database, were used to identify cohort studies on the relationship between the baseline CRP levels and ICI survival outcomes from inception to November 2020. Literature screening, data extraction and quality evaluation of studies were independently performed by two reviewers. Subsequently, a meta-analysis was performed using STATA 14.0. A total of 13 cohort studies comprising 2,387 patients with cancer were included in the present meta-analysis. The results indicated that high baseline CRP levels (serum CRP measured within 2 weeks before ICI treatment) were associated with low overall survival (OS) and progression-free survival (PFS) rate among patients treated with ICIs. The subgroup analysis based on cancer type showed that high baseline CRP levels were associated with poor survival outcomes of multiple types of cancer, such as non-small cell lung cancer (6/13; 46.2%), melanoma (2/13; 15.4%), renal cell (3/13; 23.0%) and urothelial carcinoma (2/13; 15.4%). Similar results were observed in subgroup analysis based on the CRP cut-off value of 10 mg/l. In addition, a higher mortality risk was reported in patients with cancer and CRP =10 mg/l (hazard ratio, 2.76; 95% CI, 1.70-4.48; P<0.001). Compared with patients with low baseline CRP levels, increased baseline CRP levels were associated with low OS and PFS rate in patients with cancer receiving ICIs. Furthermore, CRP =10 mg/l indicated a worse prognosis. Therefore, baseline CRP levels may serve as a marker for the prognosis of patients with certain types of solid tumor treated with ICIs. Due to the limited quality and quantity of included studies, more prospective well-designed studies are required to verify the present findings. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the leading global malignancies with low 5-year survival and high mortality rates. Despite extensive research, the precise role of gut metabolites in CRC development and clinical outcomes remains unclear, while its elucidation may aid the development of improved clinical diagnosis and treatment options. In the present study, targeted metabolomic analysis was conducted on fecal samples from 35 patients with CRC, 37 patients with colorectal adenoma and 30 healthy controls (HC) to identify metabolite biomarkers. Using orthogonal partial least squares discriminant analysis, metabolomic features distinguishing the three groups were identified. Receiver operating characteristic (ROC) curve analysis was used to assess diagnostic utility for distinguishing CRC from HC. The association of gut metabolites with survival in patients with CRC was also analyzed by comparing short-term survivors (STS) and long-term survivors (LTS), and the prognostic ability of metabolites was predicted using Cox regression and Kaplan-Meier analysis. The results of the current study showed that the enriched pathways in CRC included 'caffeine metabolism', 'thiamine metabolism', 'phenylalanine, tyrosine and tryptophan biosynthesis' and 'phenylalanine metabolism'. ROC analysis found that 9,10-dihydroxy-12-octadecenoic acid, cholesterol ester (18:2) and lipoxinA4 distinguished CRC from HC. Joint quantification of these three metabolites resulted in an area under the ROC curve of 0.969 in the diagnosis of CRC. The analysis of the current study also showed that the expression of metabolites involved in 'sphingolipid metabolism' was mainly dysregulated in LTS and STS, while N-acetylmannosamine and 2,5-dihydroxybenzaldehyde were associated with better overall survival. In conclusion, the present study provided preliminary insight into the metabolic changes associated with CRC and may have important implications for the development of future diagnostic and treatment strategies. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine Kirsten Ras sarcoma virus (KRAS) mutations and the associations of KRAS mutations with clinicopathological features and treatment outcomes in Vietnamese non-polyp colon cancer (NPCC) patients. The data in the present study covered 194 patients with non-polyp colon cancers at stages II or III, according to the 8th edition of the American Joint Committee on Cancer staging system, in northern Vietnam from January 2016 to August 2020. All patients underwent radical surgery and adjuvant therapy with FOLFOX4 or XELOX. Subsequently, the recruited patients were followed-up with scheduled hospital exams for diagnosing recurrence. Genomic DNA samples were prepared from dissected tumors and specific sequences of the KRAS gene were amplified by polymerase chain reactions (PCR). The mutations at codons 12, 13, 59, 60, 61, 117 and 146 of the gene were determined. Possible associations of the KRAS mutations with clinicopathological properties and the survival of patients were analysed. The KRAS mutation rate was 47.9% in Vietnamese patients with NPCC, of those, mutations in exon 2 accounted for 91.4% of all detected mutations. The mutated-KRAS patients exhibited a significantly higher rate of anemia. Moreover, the KRAS mutation rate was higher in females (57.1%) than in males (39.8%). The KRAS mutation rate was also higher in patients with right colon cancers. Furthermore, KRAS mutations were an independent prognosis for poor disease-free survival (DFS) and overall survival (OS) in stage II patients. Among left-sided colon patients, mutated KRAS was a significant predictive factor for poor DFS but not for OS. The present study revealed a very high mutation rate of KRAS in Vietnamese patients with NPCC. The data of the present study indicated that the mutation status was associated with female patients and right-sided tumors. The KRAS mutations were a negative factor for the survival of patients with stage II NPCC and patients with left-sided colon cancer. [ABSTRACT FROM AUTHOR]

The aim of the present study was to perform the accurate prognosis of different molecular types breast cancer (BC) by using the partitioning calculation method of the Ki-67 index. Partitioning calculation was used to judge the Ki-67 index and the molecular type was classified according to the 2019 Chinese Society of Clinical Oncology guidelines in 199 cases of BC. The association between the Ki-67 index and overall survival (OS), disease-free survival (DFS) and molecular types was analyzed using the Chi-squared test. Survival analysis was performed using the Kaplan-Meier method with statistical SPSS 18.0 software. The results revealed that the 5-year survival rate of patients with BC was 18.60% (8/43), the 6-year survival rate was 38.24% (26/68), while the 10-year survival rate of patients with BC was 73.08% (133/182); the results indicated that almost 80% patients succumbed during the 5 years following diagnosis. Marked differences were found between the OS of patients with BC and the Ki-67 index (between 50 to 54%) (χ2=4.83, P=0.028; χ2=4.60, P=0.032 respectively). All 14 cases of luminal A subtype BC with a Ki-67 index ≤4% survived at the end of follow-up time (69-156 months). At the same time, there was a marked difference between two groups of patients with overexpression HER-2 while using 50% as a cut-off point of Ki-67 (χ2=5.54, P=0.019). On the whole, the present study demonstrates that the partitioning calculation of the Ki-67 index can be used to judge the prognosis of patients with BC accurately. The prognosis of patients with different molecular subtypes of BC may be associated with the different Ki-67 index. [ABSTRACT FROM AUTHOR]

Chemotherapy is controversial in non-metastatic typical carcinoid (TC) tumors. Therefore, it was aimed to evaluate the impact of platin-based chemotherapy on the survival of patients with lung TC. The medical records of patients who underwent surgical resection for non-metastatic TC from 2002 to 2020 at our institution were retrospectively reviewed. Multivariate regression analysis was performed for chemotherapy and prognostic factors in disease-free survival (DFS) in 72 patients. The pathological stages of patients were as follows: 73.6% of the patients were in stage I, 15.3% in stage II and 11.1% in stage III. A total of 5 patients (6.9%) received platin-based chemotherapy and 6 patients (8.3%) had recurrences. The DFS rates at 12, 36 and 60 months were 98.5, 95.1 and 92.5%, respectively. Log-rank testing showed that patients who received chemotherapy and had stage III disease had shorter DFS (P=0.021 for chemotherapy and P<0.001 for stage). However, multivariate analysis revealed that the pathological stage was the only statistically significant factor affecting DFS (P=0.016). Platin-based chemotherapy did not improve DFS, and the eighth edition of TNM (tumor, nodes, metastases) staging did have prognostic value for patients with non-metastatic TC. Although resection has satisfying long-term outcomes, studies on new agents are needed to decrease the recurrence rate, particularly in patients with stage III disease. [ABSTRACT FROM AUTHOR]

The present study investigated the role of ramucirumab (RAM) in treating liver metastases (LMs) as a second-line or salvage treatment in patients with advanced CRC. Of the 36 patients, 21 (58%) received RAM plus folinic acid, fluorouracil and irinotecan (FOLFIRI) as second-line treatment, whereas 15 (42%) received it in a salvage setting. The median overall survival time was 23 months [95% confidence interval (CI), 12–34 months] for those in the second-line treatment group and 8 months (95% CI, 5–19 months) for those in the salvage treatment group. Of the 36 patients, 14 (39%) underwent surgical resection of LMs during chemotherapy. A total of 6 patients underwent surgical resection for LMs for the first time during second-line RAM plus FOLFIRI (RAM-LM); of the remaining 8 patients, 6 underwent resection of LMs during first-line bevacizumab (BEV)-based chemotherapy (BEV-LM). Immunohistochemical analysis of CD42b showed that the platelet aggregation score (CD42b score), which ranges from 0 (absence of deposition) to 3 (presence of linear deposition), tended to decrease with the increasing duration of treatment with both RAM and BEV. Although there was no significant difference in the mean duration of anti-VEGF antibody treatment between the BEV-LM and RAM-LM groups, the median CD42b score was higher in the RAM-LM group (median CD42b score, 3; range, 0–3) compared with that in the BEV-LM group (median CD42b score, 1; range, 0–3; P=0.01), suggesting that RAM induces a different degree of platelet aggregation in liver sinusoids compared to BEV. [ABSTRACT FROM AUTHOR]

The present study evaluated the efficiency, prognostic factors for and the safety of irinotecan combined with raltitrexed (TOMIRI) in patients with metastatic colorectal cancer (CRC). Outcome data of patients who received TOMIRI as first-, second- and third- or later-line treatment regimens were assessed to compare the efficacy of this regimen. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) were evaluated for each group. Kaplan-Meier curves and univariate and multivariate analyses were performed to evaluate efficacy. From January 2017 to December 2019, TOMIRI was administered as a first-line treatment in 23 patients, second-line treatment in 164 patients and third- or later-line treatment in 18 patients. Irinotecan and 5-fluorouracil (FOLFIRI) was administered to another 50 patients, who served as the control group. The median PFS was 9, 7 and 6 months and the median OS was 37, 21 and 17 months for first-, second- and third- or later-line treatments, respectively. The ORRs of the included patients were 21.7, 13.4 and 11.1%, respectively, and the DCRs were 91.3, 81.7 and 66.7%, respectively. Compared with FOLFIRI, TOMIRI as a second-line chemotherapy treatment was associated with longer survival of the patients with CRC. Further analysis demonstrated that pathologic tumor-node-metastasis category, carcinoembryonic antigen, carbohydrate antigen 19-9, treatment cycles, targeted therapy, treatment of local metastases and first-line PFS were prognostic factors for second-line treatment. Among these, the number of treatment cycles was of vital importance. Hepatic dysfunction was the most commonly reported grade 1–2 (55.1%) and grade 3–4 (7.3%) adverse event. Neutropenia (12.2%), thrombocytopenia (10.2%), anemia (27.3%), proteinuria (38.1%) and hematuria (21.0%) were also common grade 1–2 adverse events. In conclusion, TOMIRI may be recommended as an effective and safe second-line treatment for metastatic CRC in the clinic. [ABSTRACT FROM AUTHOR]

In cancer, tumor-related inflammation affects disease progression and survival outcomes. However, the role of systemic inflammation in tumor multifocality in upper tract urothelial carcinoma (UTUC) is not well understood. The aim of the present study was to evaluate the impact of the systemic inflammation response index (SIRI) on tumor multifocality for predicting oncological outcomes in patients with UTUC after radical nephroureterectomy (RNU). For this purpose, data from 645 patients with non-metastatic UTUC who underwent RNU between 2008 and 2020 were retrospectively analyzed. Survival outcomes such as overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) RATES were assessed using the Kaplan-Meier method, and independent prognostic factors were identified through a multivariable Cox proportional hazards regression model. Of the 645 patients with UTUC included in the present study, 163 (25%) had multifocal UTUC. Kaplan-Meier analysis indicated that multifocal UTUC synchronous with a high-level SIRI was significantly associated with poorer outcomes after RNU. Furthermore, the results of the multivariate Cox proportional hazards model analysis demonstrated that multifocal tumor coupled with a high-level SIRI was an independent factor for predicting a shorter survival and disease progression. In conclusion, the results of the present study indicated that an elevated SIRI significantly influenced the survival rate of patients with multifocal UTUC. Specifically, integrating multifocal UTUC with a high-level SIRI emerged as an independent risk factor for poorer OS, CSS and RFS. These findings highlighted the potential role of SIRI in the risk stratification and management of patients with multifocal UTUC. [ABSTRACT FROM AUTHOR]

Advanced melanoma is an aggressive and dangerous form of skin cancer, and programmed cell death-1 (PD-1) inhibitors are recommended treatment options for patients with advanced melanoma. Mucosa-associated lymphoid tissue 1 (MALT1) impairs CD8+ T-cell activation to induce immune escape, leading to a reduction in the antitumor effect of PD-1 inhibitors. The present study aimed to assess the prognostic implication of MALT1 in patients with advanced melanoma receiving PD-1 inhibitor monotherapy. Blood MALT1 levels were assessed using reverse transcription-quantitative PCR in 20 healthy controls (HCs) after enrollment and in 49 patients with advanced melanoma before (T0), as well as 2 months (T1) and 4 months after (T2) PD-1 inhibitor monotherapy. The maximum level of MALT1 in HCs (3.100) was used as the cut-off in patients with advanced melanoma. MALT1 levels at T0 were significantly increased in patients with advanced melanoma compared with in HCs (P<0.001). In patients with advanced melanoma, MALT1 was significantly decreased from T0 to T2 (P<0.001). Objective response rate (ORR) and disease control rate (DCR) were 28.6 and 59.2%, respectively. MALT1 levels at T1 were significantly negatively associated with overall therapeutic response (P=0.001), ORR (P=0.009) and DCR (P=0.004). MALT1 levels at T2 were significantly inversely associated with overall therapeutic response (P=0.021) and ORR (P=0.036). Moreover, MALT1 levels >3.100 at T0 (P=0.027) and T1 (P=0.045) were significantly associated with shorter progression-free survival (PFS), and MALT1 levels >3.100 at T1 were significantly associated with a poor overall survival (OS; P=0.022). Multivariate Cox regression analysis demonstrated that MALT1 levels at T0 (>3.100 vs. ≤3.100) were significantly associated with a poor PFS [hazard ratio (HR)=2.248; P=0.037], and MALT1 levels at T1 (>3.100 vs. ≤3.100) were significantly associated with a poor OS (HR=4.332; P=0.007). In conclusion, MALT1 levels are reduced following PD-1 treatment, and a high MALT1 level is associated with a poor therapeutic response and shorter survival in patients with advanced melanoma receiving PD-1 inhibitor monotherapy. [ABSTRACT FROM AUTHOR]

Chemotherapy has helped prolong survival in patients with malignant lymphoma, enhancing their quality of life (QOL). Despite the eventual decline in the QOL of patients, the impact of initial chemotherapy remains poorly understood. A prospective patient-reported QOL survey among patients with malignant lymphoma receiving initial chemotherapy was conducted, targeting those treated at Gifu Municipal Hospital (Gifu, Japan) between January 2021 and December 2022. Surveys were conducted pre- and post-chemotherapy based on the EuroQol 5 dimensions. Drug costs were calculated using official prices and analyzed from the cost payer's perspective via cost-utility analysis. Among the 60 patients included in the present study, 28 had diffuse large B-cell lymphoma. Cyclophosphamide, doxorubicin, vincristine, prednisolone ± rituximab therapy was the most common treatment (38 patients) and demonstrated superior cost-effectiveness due to its lowest cost and change in utility value. Initial chemotherapy for patients with malignant lymphoma generally improved the QOL. Clinical trial registration: UMIN000042868 (registered on December 28, 2020). [ABSTRACT FROM AUTHOR]

The present systematic review and meta-analysis aimed to compare long-term survival after proximal gastrectomy (PG) and total gastrectomy (TG) for locally advanced proximal gastric cancer (GC). The PubMed, EMBASE and Cochrane CENTRAL databases were searched from their inception to May 2023. Only published two-arm prospective or retrospective studies were included. The selected studies included patients with locally advanced GC who underwent PG or TG and reported quantitative survival outcomes. The primary outcome was overall survival (OS) after gastrectomy. Three studies involving a total of 4,815 patients met the inclusion criteria. The age of the patients ranged from 57.03–64.46 years and 78.80% were male. The estimated 5-year OS probability after TG varied from 30.14 to 72.0%, and from 42.06 to 74.9% after PG. Results of the meta-analyses revealed a significant association between PG and improved OS compared with that of TG, with a pooled hazard ratio of 1.15 (95% CI, 1.05–1.25). No heterogeneity was observed in the included studies (I2=0%). Overall, in managing locally advanced GC, PG demonstrated comparable or marginally improved OS compared with TG during postoperative follow-up; however, further meta-analyses are required to provide stronger evidence. [ABSTRACT FROM AUTHOR]

Solute carrier family 20 member 1 (SLC20A1) is a sodium/inorganic phosphate symporter, which has been identified as a prognostic marker in several types of cancer, including pancreatic cancer. However, to the best of our knowledge, the association between SLC20A1 expression and cancer stem cell (CSC) markers, such as aldehyde dehydrogenase 1 (ALDH1), in pancreatic ductal adenocarcinoma (PDAC), and the role of SLC20A1 in PDAC CSCs remains unclear. In the present study, a genomic dataset of primary pancreatic cancer (The Cancer Genome Atlas, Pan-Cancer Atlas) was downloaded and analyzed. Kaplan-Meier analysis and multivariate Cox regression analysis were performed to evaluate the overall survival, disease-specific survival (DSS), disease-free interval (DFI) and progression-free interval (PFI). Subsequently, SLC20A1 small interfering RNA (siRNA) knockdown (KD) was induced in the PANC-1 and MIA-PaCa-2 PDAC cell lines, and in sorted high ALDH1 activity (ALDH1high) cells, after which, cell viability, in vitro tumor sphere formation, cell death and caspase-3 activity were examined. The results revealed that patients with high expression of SLC20A1 (SLC20A1high) at tumor stage I had a poor prognosis compared with patients with low expression of SLC20A1 (SLC20A1low) in terms of DSS, DFI and PFI. In addition, patients with high expression of SLC20A1 and ALDH1A3 (SLC20A1highALDH1A3high) exhibited poorer clinical outcomes than patients with high expression of SLC20A1 and low expression of ALDH1A3 (SLC20A1highALDH1A3low), low expression of SLC20A1 and high expression of ALDH1A3 (SLC20A1lowALDH1A3high) and SLC20A1lowALDH1A3low. SLC20A1 siRNA KD in ALDH1high cells isolated from PANC-1 and MIA-PaCa-2 cell lines resulted in suppression of in vitro tumorsphere formation, and enhancement of cell death and caspase-3 activity. These results suggested that SLC20A1 was involved in cell survival via the suppression of caspase-3-dependent apoptosis, and contributed to cancer progression and poor clinical outcomes in PDAC. In conclusion, SLC20A1 may be used as a prognostic marker and novel therapeutic target of ALDH1-positive pancreatic CSCs. [ABSTRACT FROM AUTHOR]

The Stupp regimen remains the standard treatment for newly diagnosed glioblastomas, although the prognosis remains poor. Several temozolomide alternative schedules have been studied, with extended adjuvant treatment (>6 cycles of temozolomide) frequently used, although different trials have indicated contrasting results. Survival data of 87 patients who received 6 ('6C' group) or 12 ('12C' group) cycles of temozolomide were collected between 2012 and 2022. A total of 45 patients were included in the 6C group and 42 patients were included in the 12C group. Data on isocitrate dehydrogenase mutation and methylguanine-DNA-methyltransferase (MGMT) promoter methylation status were also collected. The 12C group exhibited statistically significantly improved overall survival [OS; 22.8 vs. 17.5 months; hazard ratio (HR), 0.47; 95% CI, 0.30–0.73; P=0.001] and progression-free survival (15.3 vs. 9 months; HR, 0.39; 95% CI, 0.25–0.62; P=0.001). However, in the subgroup analysis according to MGMT status, OS in the 12C group was significantly superior to OS in the 6C group only in the MGMT unmethylated tumors. The present data suggested that extended adjuvant temozolomide appeared to be more effective than the conventional six cycles. [ABSTRACT FROM AUTHOR]

Recently, the relationship between the relative dose intensity (RDI) and efficacy was demonstrated for lenvatinib therapy in patients with advanced hepatocellular carcinoma (HCC), with a higher RDI of lenvatinib monotherapy indicating a higher efficacy. However, not every patient can tolerate a high RDI during the course of treatment; therefore, add-on combination therapy may be necessary for patients requiring a low RDI. The addition of transarterial chemoembolization (TACE) to lenvatinib therapy improves clinical outcomes. Therefore, the aim of the present study was to compare the clinical outcomes of lenvatinib plus TACE (the LEN-TACE group) with those of lenvatinib alone (the LEN group) in patients with unresectable HCC with a high- or low-RDI. A total of 66 patients with advanced HCC were enrolled in the present retrospective study. Eligible patients were those who initiated lenvatinib monotherapy between April 2018 and September 2020. Of these patients, 29 had an 8-week RDI of ≥60%, 6 of which received LEN-TACE. A further 37 patients had an 8-week RDI of <60%, 7 of which received LEN-TACE. In the high-RDI group, both the radiological evaluations and the overall survival (OS) time were improved in those in the low-RDI group. In addition, the median OS of patients treated with LEN-TACE was longer compared with that of patients treated with lenvatinib alone in the low-RDI group (P=0.0467). Therefore, the results of the present study revealed that early TACE should be considered instead of continuing lenvatinib only treatment in patients receiving an insufficient dose of lenvatinib, such as those with an 8-week RDI of <60%. [ABSTRACT FROM AUTHOR]

Cervical cancer is a major global health concern. Prognostic markers for cervical cancer have traditionally focused on tumor characteristics. However, there is a growing recognition of the importaxnce of the nutritional status of the patient as a possible prognostic indicator. The present meta-analysis aims to estimate the role of the prognostic nutritional index (PNI) in predicting overall survival (OS) and progression-free survival (PFS) in patients with cervical cancer. Medline, Google Scholar, Science Direct and Cochrane Central databases were systematically searched for studies reporting PNI in patients with cervical cancer. Inclusion criteria were applied to select relevant studies and data extraction was performed by two independent investigators. Risk of bias was assessed by the Newcastle-Ottawa Scale (NOS). The present meta-analysis included 10 studies with 2,352 participants. The pooled analysis showed that in patients with cervical cancer PNI did not have a significant prognostic utility in predicting OS [univariate hazard ration (HR): 1.38; 95% confidence interval (CI): 0.77-2.48) or PFS (univariate HR: 1.12; 95% CI: 0.44-2.68). These results were consistent even after adjusting for other confounders using multivariate analysis (pooled HR: 1.06 for OS; 95% CI: 0.64-1.76; pooled HR: 1.22 for PFS; 95% CI: 0.65-2.30). Subgroup analyses were also performed based on region, PNI cut-off, sample size, grade of evidence and treatment protocol and did not demonstrate any significant prognostic value of PNI. The funnel plot demonstrated symmetry, suggesting the absence of publication bias. The present meta-analysis indicated that PNI does not have a significant prognostic utility in predicting OS or PFS in women with cervical cancer. Further research is warranted to explore alternative nutritional indicators and identify reliable prognostic markers in this patient population. [ABSTRACT FROM AUTHOR]

Transcatheter arterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) and camrelizumab (collectively: T-T-C) is a novel treatment strategy for unresectable hepatocellular carcinoma (HCC). The present systematic review and meta-analysis aimed to evaluate the efficacy and safety of T-T-C compared with TACE combined with TKIs only (T-T) in the treatment of patients with unresectable HCC. A systematic literature search was conducted on T-T and T-T-C using PubMed, Embase and the Cochrane Library. Data regarding the clinical outcome, including overall survival (OS), progression-free survival (PFS), tumor response and adverse events (AEs), were independently extracted and analyzed by two researchers using standardized protocols. In total, 7 cohort studies, including 1,798 patients (T-T-C, 838; T-T, 960), were included in the meta-analysis. The results of the present study demonstrated that the T-T-C group had significantly prolonged OS [hazard ratio (HR), 0.38; 95% confidence interval (CI), 0.29–0.50; I2=61.5%; P=0.016)] and PFS (HR, 0.37; 95% CI, 0.30–0.46; I2=44.5%; P=0.109), and showed significantly higher objective response rates [risk ratio (RR), 0.82; 95% CI, 0.69–0.96; I2=25.1%; P=0.237)] and slightly higher disease control rates without a significant difference (RR, 0.96; 95% CI, 0.89–1.03; I2=0.0%; P=0.969). In addition, grade 3/4 AEs were more common in the T-T group, including hypertension (RR, 1.15; 95% CI, 0.85–1.56), vomiting or nausea (RR, 0.88; 95% CI, 0.44–1.76) and pain (RR, 0.74; 95% CI, 0.45–1.21); however, these results were not statistically significant. In conclusion, compared with T-T combination therapy, T-T-C demonstrated a notable advantage in terms of OS, PFS, ORR and DCR in patients with unresectable HCC. For manageable AEs, although the results were not statistically significant, the incidence of AEs in the T-T group was higher than that in the T-T-C group in terms of event probability. [ABSTRACT FROM AUTHOR]

The mediator complex (MED) family is a contributing factor in the regulation of transcription and proliferation of cells, and is closely associated with the development of various types of cancer. However, the significance of the expression levels and prognostic value of MED genes in kidney renal clear cell carcinoma (KIRC) have rarely been reported. The present study analyzed the expression and prognostic potential of MED genes in KIRC. The Search Tool for the Retrieval of Interacting Genes/Proteins was used to construct the protein-protein interaction network (PPI), the Assistant for Clinical Bioinformatics database was used to perform correlation analysis, GEPIA 2 was utilized to draw the Kaplan-Meier plot and analyze prognostic significance and the Tumor Immune Estimation Resource was used to assess the association of MED genes with the infiltration of immune cells in patients with KIRC. A total of 30 MED genes were identified, and among these genes, 11 were selected for the creation of a prognostic gene signature based on the results of a LASSO Cox regression analysis. Furthermore, according to univariate and multivariate analyses, MED7, MED16, MED21, MED25 and MED29 may be valuable independent predictive biomarkers for the prognosis of individuals with KIRC. Furthermore, there were significant differences in the expression levels of MED7, MED21 and MED25 in KIRC among different tumor grades. Additionally, patients with KIRC with high transcription levels of MED7, MED21 and MED29 had considerably longer overall survival times. The expression levels of MED genes were also linked to the infiltration of several immune cells. Overall, MED genes may have potential significance in predicting the prognosis of patients with KIRC. [ABSTRACT FROM AUTHOR]

Kinesin family protein 2A (KIF2A) is a microtubule depolymerase that participates in the progression of various cancers; however, its clinical utility in endometrial carcinoma (EC) remains unclear. The aim of the present study was to assess KIF2A expression and its relationship with prognosis in patients with EC. Data from 230 patients with EC who underwent tumor resection were reviewed in the current, retrospective study. KIF2A expression was measured in 230 formalin-fixed paraffin-embedded (FFPE) specimens of tumor tissue and 50 FFPE specimens of non-tumor tissue using immunohistochemistry (IHC). KIF2A expression was elevated in EC tumor tissue vs. non-tumor tissue (P<0.001). Furthermore, tumor KIF2A expression was linked with lymphovascular invasion (P=0.004) and higher International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.001). High tumor KIF2A expression (IHC score>3) was correlated with shorter disease-free survival (DFS; P=0.014) and overall survival (OS; P=0.012). Moreover, the time-dependent receiver operating characteristic curves revealed that tumor KIF2A expression had an acceptable use for estimating the relapse and death risks at each timepoint within 6 years, with each area under the curve remaining stable at ≥0.7. Notably, tumor KIF2A expression (high vs. low) independently forecast shorter DFS (hazard ratio, 2.506; P=0.013), but not OS (P>0.05). Furthermore, information from The Human Protein Atlas database indicated that high tumor KIF2A expression was associated with worse OS in patients with EC (P=0.027). Tumor KIF2A is not only associated with lymphovascular invasion and higher FIGO stage, but also reflects unfavorable survival in patients with EC. [ABSTRACT FROM AUTHOR]

Despite the high prevalence of localised prostate cancer (LPC) and locally advanced prostate cancer (LAPC), evidence on the characteristics of patients, treatments and clinical outcomes stratified by disease risk is limited. The PEarlC study was conducted to characterise a cohort of patients with early-stage prostate cancer that included real-world clinical outcomes. Retrospective data from a cohort of patients diagnosed with LPC/LAPC between 2015 and 2017 and followed up until December 2020 at a Portuguese comprehensive cancer centre (IPO Porto) was analysed. Patients were classified as LPC (high- or non-high-risk) or LAPC according to European Association of Urology guidelines, were eligible if diagnosed at stage I–III and followed up in Urology, Medical Oncology or Radiation Oncology outpatient clinics of IPO Porto. Data was collected from the medical/administrative records database. Clinical outcomes included prostate-specific antigen (PSA) progression-free survival, metastasis-free survival, disease-free survival, progression-free survival, overall survival (OS), PSA response (palliative) and no evidence of residual tumour (prostatectomy). Time-to-event outcomes were compared between subgroups using the log-rank test. A total of 790 patients were included (54.8% non-high-risk LPC, 30.9% high-risk LPC, 14.3% LAPC) and the median follow-up was 46.7 months. Patients had a median age of 68.0 years. The majority of patients were stage II (52.9%) and Eastern Cooperative Oncology Group 0–1 (99.9%) and received treatment with curative intent (85.4%). The median was only achieved in progression-free survival (29.9 months; 95% CI, 26.5–41.0 months), as evaluated in palliative patients. At year 5, 82.9% were free of PSA progression (curative), 87.5% were metastasis-free, 83.7% were disease-free, all patients in palliative treatment progressed and the 5-year OS rate was 92.9% (CI 95%, 90.2–95.7%). Among patients with LPC, OS was worse in high-risk vs. non-high-risk patients (5-year OS rate, 88.8% vs. 96.8%; hazard ratio=3.34, CI 95%, 1.64–7.05; P=0.001). PSA response rate was 81.4% in the palliative setting. There was no evidence of residual tumour in 61.6% of patients who underwent prostatectomy. Although most patients with early-stage prostate cancer treated at IPO Porto showed positive 5-year real-world outcomes, patients with high-risk LPC showed worse OS compared with patients with non-high-risk LPC and therefore a poorer prognosis. The present large-sample real-world study is an important contribution to reducing the evidence gap on prostate cancer. [ABSTRACT FROM AUTHOR]

The inflammatory status of patients is closely related to their nutritional status, and the impact of inflammatory status on patients with pyloric stenosis remains unclear. The present study aimed to investigate the impact of inflammatory status on the prognosis of patients with gastric cancer with early pyloric stenosis who underwent radical resection. A retrospective analysis included 242 patients with gastric cancer who underwent radical resection at the Affiliated Hospital of Southwest Medical University between July 2016 and December 2020. All patients were diagnosed with early pyloric stenosis. Correlation analysis was used to assess variations among different factors, and survival analysis was conducted to evaluate differences in overall survival (OS). To identify independent prognostic indicators, both univariate and multivariate Cox regression analyses were performed, addressing potential multicollinearity using Lasso analysis. Propensity score matching (PSM) was employed to eliminate potential confounding factors. Additionally, a prognostic risk model and nomogram based on inflammatory indicators were developed to comprehensively explore their impact on prognosis. Initial survival analysis revealed significant associations between neutrophil-to-lymphocyte ratio (NLR; χ2=10.522, P<0.001), systemic immune-inflammation index (SII; χ2=6.733, P=0.025), systemic inflammation response index (SIRI; χ2=15.490, P<0.001) and OS of the patients, while there was no significant survival difference among patients with different platelet-to-lymphocyte ratio (PLR; χ2=2.561, P=0.050). SIRI not only had the highest area under the curve but was also found to be an independent prognostic indicator (hazard ratio=1.851, P=0.046) in the present study. Following PSM on SIRI, a total of 174 patients were included in the subsequent analysis. Time-receiver operating characteristic and survival curves for SIRI after PSM consistently demonstrated its robust prognostic predictive capability. Furthermore, the prognostic risk model based on SIRI and the nomogram incorporating SIRI both exhibited high prognostic value. Inflammatory status was significantly associated with the prognosis of patients with gastric cancer with early pyloric stenosis who underwent radical resection. The NLR, SII and SIRI could all predict patient outcomes. Moreover, SIRI exhibited the highest prognostic value among the inflammatory indices and has been identified as an independent prognostic factor in the present study. [ABSTRACT FROM AUTHOR]

It is unclear if premorbid use of beta-blockers affects sepsis outcomes. The present systematic review aimed to assess the impact of premorbid beta-blocker use on mortality and the need for mechanical ventilation in patients with sepsis. Embase, Scopus, PubMed and Web of Science were searched for studies comparing outcomes of patients with sepsis based on the premorbid use of beta-blockers. The primary outcome was mortality, and the secondary outcome was the need for mechanical ventilation. The results were reported as odds ratios (ORs) with 95% confidence intervals (CIs). A total of 17 studies including 64,586 patients with sepsis were included. Of them, 8,665 patients received premorbid beta-blockers and 55,921 patients were not treated with premorbid beta-blockers and served as a control group. Pooled analysis of mortality rates revealed that premorbid use of beta-blockers did not affect in-hospital mortality (OR: 0.96; 95% CI: 0.78, 1.18; and I2=63%) but significantly reduced one-month mortality rates (OR: 0.83; 95% CI: 0.72, 0.96; and I2=63%). Combined analysis of adjusted data showed that premorbid beta-blockers were associated with a significant survival advantage in patients with sepsis (OR: 0.81; 95% CI: 0.72, 0.92; and I2=70%). However, there was no effect of premorbid use of beta-blockers on the need for mechanical ventilation (OR: 0.93; 95% CI: 0.66, 1.30); and I2=72%). The results of the present study indicated that premorbid use of beta-blockers is associated with improved survival in patients with sepsis. However, it does not impact the need for mechanical ventilation. The results should be interpreted with caution as the data is observational and unadjusted. [ABSTRACT FROM AUTHOR]

The present study compared the efficacy and safety of regorafenib plus programmed death-1 inhibitors (R-P) with regorafenib monotherapy as second-line therapies for advanced hepatocellular carcinoma (HCC). A systematic search of relevant literature published in PubMed, Embase, Web of Science and Cochrane Library databases until October 2023 was conducted. Two authors independently performed data extraction and screening using standardized protocols. Stata/MP 17.0 was used for the meta-analysis to evaluate the impact of R-P treatment on major outcome indicators, including overall survival, progression-free survival (PFS), tumor response and adverse reactions, in patients with advanced HCC. The results indicated that five cohort studies involving 444 patients with advanced HCC were included. The results revealed that R-P treatment improved overall survival [hazard ratio (HR), 0.61; 95% confidence interval (CI) 0.48–0.77; I2=0.0%; P=0.663] and PFS (HR, 0.51; 95% CI 0.41–0.63; I2=17.5%; P=0.303). Additionally, it increased the objective response rate (risk ratio, 2.33; 95% CI, 1.49–3.64; I2=0.0%; P=0.994) and disease control rate (HR, 1.40; 95% CI, 1.20–1.63; I2=0.0%; P=0.892) compared with those of regorafenib. However, R-P treatment was associated with an increased incidence of adverse events, such as hypothyroidism, thrombocytopenia and rash, compared with that in regorafenib. In conclusion, R-P is superior to regorafenib monotherapy in terms of survival benefits and tumor response. [ABSTRACT FROM AUTHOR]

Fibroblast growth factors (FGFs) have a key role in various critical steps of tumor growth and progression through effects on angiogenesis, inflammation and the growth and invasion of malignant cells. Nevertheless, the role of the FGF family in human glioblastoma (GBM) has been rarely studied. The objective of the present study was to assess the RNA expression of all FGF family members in tissues obtained from patients with GBM and to analyze the association between FGF expression and the survival of these patients. For this, the RNA expression of FGF family members in the malignant and proximal tissues of 12 patients with GBM was determined by analyzing high-throughput RNA transcriptome sequencing data uploaded to the National Center for Biotechnology Information database. The relationship between FGF genes and the survival of patients with GBM and glioma was also respectively studied by analyzing data from The Cancer Genome Atlas database using the Gene Expression Profiling Interactive Analysis tool. The results showed that the expression of FGF1, FGF17, FGF20 and FGF22 in GBM tissues was lower than that in adjacent tissues, with a difference of >2 times. Analysis of the overall survival of patients with GBM indicated there were no significant relationships between the expression of FGF1, FGF17, FGF20, FGF22 and overall survival. Analysis of the overall survival of patients with glioma showed that glioma patients with low FGF1 expression achieved a longer survival time than patients with high FGF1 expression; however, high expression of FGF17 and FGF22 indicated a longer survival time. In summary, the results of the present study demonstrated the panoramic expression of FGF family members in patients with GBM, and indicated that FGF1, FGF17 and FGF22 did not affect the survival of patients with GBM, but had a notable influence on the survival of patients with glioma. [ABSTRACT FROM AUTHOR]

Peritoneal carcinomatosis is one of the leading causes of death in patients with gastrointestinal cancer. Newer locoregional treatment concepts include pressurized intraperitoneal aerosol chemotherapy (PIPAC), the regional application of pressurized chemotherapeutic agents to the abdominal cavity, which is usually performed every 4 to 8 weeks. One of the main challenges of PIPAC therapy remains the objective assessment of treatment response. The present study describes a new scoring system to histologically assess the regression of peritoneal cancer following PIPAC therapy, quantitative assessment of histological regression in peritoneal carcinomatosis (QARP). Peritoneal biopsies from 27 patients with peritoneal metastases undergoing PIPAC were obtained and processed in a standardized fashion. Biopsies were scored according to the QARP grading system. The five-tiered system was graded as follows, Grade 0, no residual tumor cells with regressive changes present; grade 1, 1–25% viable tumor cells per tumor focus with regressive changes present; grade 2, 26–50% viable tumor cells per tumor focus with regressive changes present; grade 3, 51–75% viable tumor cells per tumor focus with few regressive changes; grade 4, >75% viable tumor cells per tumor focus with minimal or no regressive changes. Based on the new grading system, the study cohort was divided into QARP responders and QARP non-responders following PIPAC treatment. Higher QARP scores were significantly correlated with higher PCI scores (r=0.32; P=0.007). However, no difference in overall survival was detected between QARP responders and QARP non-responders. Further studies are required to ascertain the reproducibility and prognostic significance of QARP. [ABSTRACT FROM AUTHOR]

Low-grade serous ovarian cancer (LGSOC) is a very rare histological subtype of serous ovarian cancer, representing ~2% of all epithelial ovarian cancer cases. LGSOC has a better prognosis but a lower response rate to chemotherapy in comparison to high-grade serous ovarian carcinoma (HGSOC). The present study is a retrospective review of the medical records of all patients with histologically proven LGSOC diagnosed and treated in a single institute between January 2003 and December 2019. A total of 23 patients diagnosed with LGSOC and treated at King Faisal Specialist Hospital and Research Center (Riyadh, Saudi Arabia) were identified. The median age at diagnosis was 45.5 years (range, 26-66 years) and the median body mass index was 26.1 (range, 18-43). A total of 21 patients (91.3%) had de novo LGSOC, whereas only 2 patients (8.7%) had LGSOC that had transformed from serous borderline ovarian tumors and recurred. A total of 8 patients (34.8%) were diagnosed with International Federation of Gynecology and Obstetrics stage IV, whereas 3 (13.0%), 3 (13.0%) and 9 (39.1%) were diagnosed with stages I, II and III, respectively. In addition, 10 (43.5%), 5 (21.7%), and 3 (13.0%) patients had complete response, stable disease and partial response statuses after first-line therapy, respectively. At a median follow-up time of 34 months [95% confidence interval (CI), 25.32-42.69], the median progression-free survival (PFS) time was 75.2 months (95% CI, 17.35-133.05) and the median overall survival (OS) time was not reached. In conclusion, LGSOC exhibited better PFS and OS times than HGSOC as compared with data from the literature, and there is the option for systemic treatment (chemotherapy or hormonal therapy). Optimal cytoreduction showed numerically higher, but non-significant, PFS and OS times compared with suboptimal debulking; however, the optimal systemic chemotherapy or hormonal treatment remains controversial. [ABSTRACT FROM AUTHOR]

Superior mesenteric artery‑first approach has been proposed for the surgical treatment of pancreatic head cancer. However, little is known about its effects on resectable pancreatic head cancer. In the present study, data from patients with resectable pancreatic head cancer, who underwent radical pancreatoduodenectomy with or without the superior mesenteric artery‑first approach at from January, 2014 to December, 2019, were retrospectively collected and analyzed. A total of 204 patients were included in the study. The blood loss and blood transfusion of the arterial approach group (n=94) were less than those of the conventional approach group (n=110). Diarrhea occurred in 31 cases (15.2%) of the arterial approach group and in 18 cases (8.8%) of the conventional approach group (P<0.05). A higher rate of R0 resection and a higher number of lymph nodes harvested were achieved in the arterial approach group (P<0.05). The 1‑, 2‑ and 3‑year tumor‑free survival rates of the patients in the arterial approach group were 60.9, 43.2 and 37.9%, respectively, and those of the patients in the conventional approach group were 64.2, 24.9 and 15.6%, respectively (P<0.05). Moreover, the 1‑, 2‑, and 3‑year overall survival rates of the patients in the arterial approach group were 79.5, 49.7 and 36.7%, and those of the patients in the conventional approach group were and 75.9, 38.6 and 18.7%, respectively (P<0.05). On the whole, the present study demonstrates that the superior mesenteric artery‑first approach can reduce intraoperative blood loss and consequent blood transfusion, facilitate the achievement of an R0 resection, and thus prolong the survival of patients, despite resulting in a higher rate of diarrhea. [ABSTRACT FROM AUTHOR]

Adenylate kinase 4 pseudogene 1 (AK4P1) is a processed pseudogene whose function in cancer biology remains largely underexplored. Bioinformatics analysis suggested an association between the expression levels of adenylate kinase 4 (AK4) gene and AK4P1, as well as a clinical significance in relation to the increased transcription levels of AK4P1 in pancreatic adenocarcinoma (PAAD). In the present study, the expression levels of AK4P1 and AK4 were compared by RT-qPCR and western blotting between PAAD tissue and paired adjacent tissue. The level of AK4P1 transcript was compared between the circulating exosomes derived from patients with PAAD and those derived from healthy donors. Overall survival of the patients with PAAD with high or low expression levels of AK4P1 or AK4 was compared. AK4 gene expression level, in vitro cell viability and gemcitabine-induced apoptosis in PAAD cells with or without AK4P1 overexpression were also assessed using Cell Counting Kit-8 and TUNEL assays. It was identified that the transcription level of AK4P1 and the expression level of AK4 in PAAD tissue were significantly higher compared with those in paired non-cancerous tissue specimens. Transcription levels of AK4P1 and AK4 showed a significant relationship in PAAD. Circulating exosomes derived from patients with PAAD showed significantly higher level of AK4P1 transcript compared with that from circulating exosomes derived from blood samples of healthy donors. Patients with high expression of AK4P1 or AK4 exhibited significantly reduced overall survival compared with those with low expression. AK4P1 overexpression significantly upregulated the expression levels of AK4 in PAAD cells and rescued the viability and survival under gemcitabine challenge decreased by AK4 knockdown but not that by AK4 knockout. Treatment with exosomes secreted by AK4P1-overexpressing PAAD cells but not with those secreted by wild-type PAAD cells significantly increased the viability and survival under gemcitabine challenge of the recipient cells. These results suggested that AK4P1 affects the cellular biological functions of PAAD cells in vitro by upregulating the expression level of AK4. AK4P1 transcripts with elevated expression levels can be transmitted between PAAD cells through exosomes and exert pro-oncogenic effects in recipient cells. [ABSTRACT FROM AUTHOR]

Cancer cells exhibit a distinct metabolic profile that features an upregulation of less efficient glycolysis accompanied by lactate production for energy generation, in contract to the characteristic metabolism of normal cells. Consequently, cancer research has focused on the enzymes that participate in these cancer metabolic pathways. Among them, hexokinase 2 (HK2) has an important position as the initial enzyme in the glycolytic pathway. Increased expression levels of HK2 have been correlated with an increased risk of poor patient outcomes and advanced tumor stages in a number of malignant tumors, such as gastric carcinoma. The present study aimed to investigate the specific role of HK2 in patients diagnosed with esophageal adenocarcinoma. A total of 643 patients with esophageal adenocarcinoma were included. Immunohistochemical staining and HK2 mRNA in situ probes were used to investigate the association of HK2 expression levels with clinical and molecular tumor characteristics. Patients who exhibited high HK2 expression levels demonstrated significantly reduced overall survival (OS) times compared with patients who exhibited low HK2 expression levels (29.6 vs. 39.9 months, respectively; P=0.027). Furthermore, high HK2 expression levels were demonstrated to be an independent risk factor for reduced patient survival (hazard ratio, 1.65; 95% CI, 1.09–2.50; P=0.018). Significantly reduced patient survival was also demonstrated in the subgroups of male patients, patients with primarily resected tumors, patients with HER2-negative tumors and patients with tumors exhibiting Y chromosome loss. Elevated expression of HK2 was identified as a risk factor for unfavorable patient survival in esophageal adenocarcinoma. This revelation suggests the potential for future diagnostic and therapeutic avenues tailored to this specific patient subset. Identifying patients with high HK2 expression may pinpoint a higher-risk cohort, paving the way for comprehensive prospective studies that could advocate for intensified monitoring and more aggressive therapeutic regimens. Furthermore, the targeted inhibition of HK2 could hold promise as a strategy to potentially enhance patient outcomes. [ABSTRACT FROM AUTHOR]

Given the limited treatment options and high mortality rates associated with gastric cancer, there is a need to explore novel therapeutic options. The present study aimed to investigate the efficacy of lenvatinib, a multi-target tyrosine kinase inhibitor, in mitigating the progress of gastric cancer in vitro. Comprehensive analyses were conducted to assess the impact of lenvatinib on gastric cancer cells, focusing on the inhibition of viability, suppression of proliferation, induction of apoptosis and reduction of metastatic potential. The effects of lenvatinib on these activities were determined using 5-ethynyl-2′-deoxyuridine staining, colony formation assay, flow cytometry, western blotting, scratch assay and Transwell assay. In addition, bioinformatics analyses were employed to identify key regulatory targets of lenvatinib, with particular attention given to platelet-derived growth factor receptor β (PDGFRB). In addition, the effects of PDGFRB overexpression on the regulation of lenvatinib were explored. Lenvatinib demonstrated significant inhibitory effects on the viability, proliferation and metastatic capabilities of MKN45 and HGC27 gastric cancer cell lines. Bioinformatics analyses identified PDGFRB as a crucial target of lenvatinib, with its downregulation showing promise in enhancing overall survival rates of patients with gastric cancer. By contrast, PDGFRB overexpression reversed the effects of lenvatinib on cells. The present findings underscore the potential of lenvatinib as a promising therapeutic option in the treatment of gastric cancer. By elucidating its mechanism of action and identifying PDGFRB as a primary target, the present study may aid further clinical advancements. [ABSTRACT FROM AUTHOR]

The present study investigated the prognosis of patients who received palliative radiotherapy (RT) for bone metastases (BMs) from renal cell cancer (RCC), and assessed the prognostic factors specific to BMs from RCC. A total of 109 patients with RCC and BMs who underwent RT for the first time were included in the study. Prognostic factors were evaluated using multivariate analysis and a scoring system based on regression coefficients was devised. The median follow-up time was 9 months, and the 0.5-year overall survival (OS) rate was 73.0%. In the multivariate analysis, the significant prognostic factors were higher performance status (≥2), no control of the primary site, disseminated metastasis, lymph node metastasis and multiple BMs. A score of 1 point was assigned to each risk factor. The median OS times were 19.0 and 5.0 months in patients with a total score of ≤1 (n=49) and >1 (n=60), respectively (P<0.01). In conclusion, a comprehensive prognostic assessment using these factors may be useful for predicting the prognoses of patients with BMs from RCC. In addition, this scoring system may be useful in selecting the optimal RT dose. [ABSTRACT FROM AUTHOR]

Treatment modalities involving an immune-checkpoint-inhibitor (ICI) have emerged as therapeutic options in advanced hepatocellular carcinoma (HCC). Nonetheless, auxiliary biomarkers are required to evaluate their efficacy. The present study aimed to assess the potential of blood mucosa-associated lymphoid tissue 1 (MALT1) in reflecting clinical response and prognosis in patients with advanced HCC who received ICI therapy. Peripheral blood was collected from 51 patients with advanced HCC who were about to receive ICI or ICI-based treatment. Blood MALT1 levels were determined using reverse transcription-quantitative PCR, and the blood MALT1 levels in 50 healthy controls (HCs) were also assessed. Besides, the treatment response and survival data were collected. The Wilcoxon rank-sum test was used for comparison analysis and the Spearman's rank correlation coefficient test was used for correlation analysis. The prognostic value of MALT1 was determined by Kaplan-Meier curve analysis with the log-rank test. Univariate and multivariate Cox regression models were used to identify factors associated with progression-free survival (PFS) and overall survival (OS). The results demonstrated that blood MALT1 levels were significantly increased in patients with advanced HCC compared with that in HCs (P<0.001). Blood MALT1 levels were increased in patients with portal vein invasion (vs. without portal vein invasion; P=0.010), extrahepatic disease (vs. without extrahepatic disease; P=0.026) and α-fetoprotein (AFP) ≥200 ng/ml (vs. AFP <200 ng/ml; P=0.040). After 4 cycles of ICI therapy, the objective response rate (ORR) and disease control rate (DCR) was 29.4 and 68.6%, respectively. Blood MALT1 levels were also significantly and negatively associated with the ORR (P=0.043) and DCR (P=0.004). Furthermore, PFS and OS were shortened in patients with high blood MALT1 levels (cut-off by the median) compared to those with low blood MALT1 levels. After adjusting using multivariate Cox regression models, high blood MALT1 levels were demonstrated to be a significant independent risk factor for shortened PFS [hazard ratio (HR)=2.419; P=0.009] and OS (HR=2.706, P=0.018) in patients with advanced HCC who received ICI therapy. In summary, blood MALT1 levels serve as a potential biomarker to reflect treatment response and survival in patients with advanced HCC who receive ICI therapy. [ABSTRACT FROM AUTHOR]

The importance of supraclavicular lymph node (SCLN) metastasis in cervical and upper thoracic esophageal squamous cell carcinoma (ESCC) has not been determined. The aim of the present study was to provide a detailed definition of the range of SCLN regions and to explore whether SCLNs should be considered as a regional lymph nodes for patients with cervical and upper thoracic ESCC. A retrospective analysis was performed on 230 patients with locally advanced cervical or upper thoracic ESCC who underwent radical radiotherapy and chemotherapy. The range of SCLN regions was defined in detail on contrast enhanced computed tomography images of the neck. According to whether the patient had lymph node metastasis in the supraclavicular region, the included patients were divided into two groups, and the survival differences and reasons for treatment failure between the two groups were analyzed. Of the 230 patients with ESCC, 71 (30.87%) exhibited lymph node metastases in the supraclavicular region. The median overall survival time of ESCC patients with and without SCLN metastasis was 17 and 30 months, respectively (P<0.001). After propensity score matching (PSM), the median overall survival time of ESCC patients with and without SCLN metastasis was 17 and 28 months, respectively (P<0.001). During the follow-up period, there were a total of 101 cases of failure of treatment in the irradiation field, 6 cases had esophageal metastasis in the non-irradiated field and 27 cases had regional lymph node metastasis in the non-irradiated field. In addition, there were 33 cases of metastasis to the distant lymph nodes or organs. There was no significant difference in the local treatment failure rate between the groups with or without SCLN metastasis in both the irradiation field and the non-irradiation field, but the probability of distant metastasis in the SCLN metastasis group was significantly higher than that in the group without SCLN metastasis (P=0.025). In conclusion, patients with cervical and upper thoracic ESCC with SCLN metastasis have a poor prognosis and the median overall survival time is closer to that of metastatic ESCC than ESCC with regional lymph node metastasis; therefore, SCLNs should not be defined as regional lymph nodes in patients with cervical and upper thoracic ESCC. [ABSTRACT FROM AUTHOR]

The association of computed tomography (CT)-derived skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) with postoperative prognosis in patients with gastric cancer (GC) remains unknown. Therefore, the present study aimed to assess the association between SMI and SMD with 5-year overall survival (OS) and recurrence-free survival (RFS) in patients with GC. SMI and SMD were measured preoperatively in patients who underwent gastrectomy. Patients were categorized into Groups 1 (high SMI and SMD), 2 (high SMI or SMD) and 3 (low SMI and SMD). OS and RFS rates were assessed using Kaplan-Meier analysis and the log-rank test. Among 459 patients, OS and RFS rates were significantly lower in the low-SMD group than in the high-SMD group (OS, 83.4% vs. 88.8%, respectively; P=0.04 and RFS, 80.5% vs. 87.2%, respectively; P=0.02). OS and RFS rates were also significantly lower in Group 3 than in Groups 2 and 1 (P=0.006). Multivariate analysis revealed that a low SMI and SMD (Group 3) was a significant independent prognostic factor for OS [hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.17–4.59; P=0.016] and RFS (HR, 2.28; 95% CI, 1.19–4.37; P=0.013). In summary, low SMI and SMD values may be useful postoperative prognostic indicators for patients with GC. [ABSTRACT FROM AUTHOR]

Previous studies have reported low serum creatine kinase (s-CK) levels as a poor prognostic factor in various cancers. However, there have been no reports on its significance in hepatocellular carcinoma. The present study aimed to evaluate the association of the preoperative s-CK levels with clinicopathologic features and their prognostic impact on survival in patients with hepatocellular carcinoma. This retrospective study included 163 patients with hepatocellular carcinoma (127 male and 36 female patients; median age, 69 years) who underwent radical liver resection between January 2004 and December 2021. A cutoff preoperative s-CK level of 91 U/l determined by receiver operating characteristic curve analysis was used to evaluate the significance of s-CK in predicting overall and recurrence-free survival. In addition, the prognostic impact of s-CK was evaluated using univariate and multivariate analysis. s-CK level was not associated with clinicopathologic factors. Overall survival and recurrence-free survival of the low s-CK group were significantly worse compared with the high s-CK group (P=0.043 and P=0.029, respectively). By multivariate analysis, low s-CK was an independent risk factor for poor overall survival and recurrence-free survival (P=0.019 and P=0.014, respectively). This trend was the same for male patients, but no significant difference was observed for female patients. Low preoperative s-CK level might be a poor prognostic biomarker in patients with hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

The ability of nutrition and immune-related biomarkers to predict outcomes in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant therapy followed by surgery remains controversial due to the lack of evidence regarding the accuracy and reliability of these biomarkers in predicting outcomes for such patients. Therefore, the present study aimed to investigate the prognostic potential of nutrition and immune-related biomarkers in patients with LARC who underwent chemoradiotherapy followed by curative surgery. The clinical data of patients with LARC treated with neoadjuvant therapy followed by surgery between January 2010 and December 2019 were analyzed. In total, 214 consecutive patients were enrolled into the present study, who were then categorized into low and high prognostic nutritional index (PNI) groups. The X-tile 3.6.1 program was used to calculate and then determine the optimal cut-off values for PNI. Disease-free survival (DFS) and overall survival (OS) were compared between the low and high PNI groups. Cox regression analysis demonstrated that low PNI and high post-chemoradiotherapy carcinoembryonic antigen levels were significantly associated with reduced disease-free survival and overall survival. Specifically, a low PNI was associated with inferior 5-year DFS (P=0.025) and OS (P=0.018). These findings suggest that amongst the nutritional and immune-related biomarkers, PNI is a significant predictive factor for disease recurrence and mortality in patients with LARC treated with neoadjuvant therapy followed by surgery. [ABSTRACT FROM AUTHOR]

Despite technical advances in recent decades and a decrease in hospital mortality (<5%), pancreaticoduodenectomy (PD) is still associated with major postoperative complications, even in high-volume centers. The present study aimed to assess the effect of a modified reconstruction technique on postoperative morbidity and mortality. A cohort study of all patients (n=218) undergoing PD between January 2010 and December 2019 was performed at Attikon University Hospital (Athens, Greece). Several variables were studied, including demographic data, past medical history, perioperative parameters, tumor markers and pathology, duration of hospitalization, postoperative complications, 30-day-survival, postoperative mortality and overall survival using multivariate logistic regression and survival analysis techniques. In this cohort, 123 patients [modified PD (mPD) group] underwent a modified reconstruction after a pylorus-preserving pancreaticoduodenectomy, which consisted of gastrojejunostomy and pancreaticojejunostomy on the same loop and an isolated hepaticojejunostomy on another loop. In the standard PD (StPD) group, 95 patients underwent standard reconstruction. The median age was 67 years, ranging from 25 to 89 years. Compared with in the StPD group, the mPD group had significantly lower rates of grade B and C pancreatic fistula (4.9% vs. 28.4%), delayed gastric emptying (7.3% vs. 42.1%), postoperative hemorrhage (3.3% vs. 20%), intensive care unit admission (8.1% vs. 18.9%), overall morbidity (Clavien-Dindo grade III-V: 14.7% vs. 42.0%), perioperative mortality (4.1% vs. 14.7%), and shorter hospitalization stay (11 days vs. 20 days). However, no difference was noted regarding median survival (35 months vs. 30 months). In this single-center series, a modified reconstruction after PD appears to be associated with improved postoperative outcomes. However, further evaluation in larger multi-center trials is required. [ABSTRACT FROM AUTHOR]

IL1RL2 has been reported to be highly expressed in a variety of tumor types whereas its role in bladder cancer (BLCA) remains unclear. The aim of the present study was to explore the prognostic value of Il1RL2 in BLCA and its relationship with clinical pathological features. The Cancer Genome Atlas (TCGA) database was used to assess the levels of IL1RL2 expression in BLCA tissues and cells, which were validated by reverse transcription-quantitative polymerase chain reaction and western blotting. Immunohistochemistry was employed to analyze expression of the IL1RL2 gene in 17 pairs of tumor and normal specimens, as well as 112 samples with different stages and grades of tumors. To investigate the biological functions of Il1RL2 in BLCA, co-expression networks and functional enrichment analyses were conducted. A protein-protein interaction network was constructed using interaction gene search tools. IL1RL2 was revealed to be clearly expressed in BLCA cells and tissues. The area under the curve for amplification of IL1RL2 distinguishing between tumor and normal tissues was 0.700 (95% CI: 0.579-0.821) in the TCGA database and 0.647 (95% CI: 0.497-0.797) in Miyun chart database, respectively. Furthermore, in our database, both univariate and multivariate analyses indicated that IL1RL2 expression was an independent risk factor for overall survival (OS). Kaplan-Meier survival analysis revealed an association between high IL1RL2 expression and low OS. Pathway enrichment analysis suggested that IL1RL2 is involved in the regulation of tumor progression through the MAPK signaling pathway. The expression level of IL1RL2 was associated with the stage, grade, lymph node album and prognosis of BLCA. [ABSTRACT FROM AUTHOR]

Cancer-associated thromboembolism (CAT), including venous thromboembolism (VTE) and arterial thromboembolism (ATE), is a frequent complication of advanced pancreatic cancer. However, reports on its incidence and clinical outcomes, especially on ATE, are limited. The present study aimed to investigate the incidence of CAT and its effects on overall survival in patients with metastatic pancreatic cancer. As part of the Tokushukai REAl-world data project in Japan, 846 eligible patients with metastatic pancreatic cancer treated with first-line chemotherapy were identified between April 2010 and March 2020. Using diagnosis procedure combination data from these patients, the present study investigated the incidence of VTE, ATE and cerebral and gastrointestinal bleeding requiring hospitalization. Blood laboratory data were collected within 14 days of the start of first-line treatment, and Khorana scores were calculated. The associations between CAT complications and comorbidities, concomitant medications and prognosis were examined. Among the 846 patients, 21 (2.5) and 70 (8.3%) had VTE and ATE, respectively (including five with overlapping VTE and ATE). CAT-positive patients had a significantly higher rate of gastrointestinal bleeding events compared with CAT-negative patients [13 of 86 (15.2%) vs. 46 of 760 (6.1%); P=0.01]. CAT-positive patients had a poorer prognosis [hazard ratio (HR), 1.28; 95% confidence interval (CI), 1.01-1.62] compared with CAT-negative patients, even after adjusting for background factors (HR, 1.20; 95% CI, 0.95-1.52). Cox regression analyses showed that higher Khorana scores were associated with significantly worse prognosis. This real-world data demonstrated that the incidence rate of CAT in patients with metastatic pancreatic cancer was 10.2%, and no statistically significant differences were observed, although there was a trend toward an adverse prognosis. The Khorana score may also be useful for predicting prognosis, even in the absence of CAT. This study was registered in the UMIN Clinical Trial Registry (http://www.umin.ac.jp/ctr/index.htm; clinical trial no. UMIN000050590). [ABSTRACT FROM AUTHOR]

The treatment paradigm for non-metastatic castration-resistant prostate cancer (nmCRPC) has changed in recent years. An observational multicenter study was conducted to evaluate the effectiveness of androgen receptor signaling inhibitors (ARSIs) as a first-line treatment for patients with nmCRPC. The present study included native Japanese patients from four hospitals who received ARSIs as a first-line treatment for nmCRPC. The primary endpoint of the study was to evaluate the efficacy and safety of ARSI in patients with nmCRPC. The secondary endpoint was to develop a novel system to stratify the prognoses of these patients. In total, 160 patients were included in the present study. Within a median follow-up period of 23 months, the median overall survival (OS) was not reached, whereas the median progression-free survival was 26 months. Multivariate Cox regression analyses showed that the time to CRPC, prostate-specific antigen (PSA) level at the initiation of nmCRPC treatment and Geriatric Nutritional Risk Index (GNRI) were independent predictors of OS. The patients for whom information about all three independent OS predictors was available were subsequently divided into three groups as follows: Group 1, 57 patients with negative or one positive independent OS predictor; group 2, 38 patients with two positive independent OS predictors; and group 3, 10 patients with three independent OS predictors. The OS differed significantly among the three groups (P<0.0001). In conclusion, ARSIs as a first-line treatment may be associated with favorable outcomes in Japanese patients with nmCRPC. Time to CRPC, PSA level at the initiation of nmCRPC treatment and GNRI are potential predictors of OS in Japanese patients with nmCRPC who received ARSIs as a first-line treatment. [ABSTRACT FROM AUTHOR]

Tamoxifen is a widely used anti-estrogen drug in the endocrine therapy of breast cancer (BC). It blocks estrogen signaling by competitively binding to estrogen receptor α (ERα), thereby inhibiting the growth of BC cells. However, with the long-term application of tamoxifen, a subset of patients with BC have shown resistance to tamoxifen, which leads to low overall survival and progression-free survival. The molecular mechanism of resistance is mainly due to downregulation of ERα expression and abnormal activation of the PI3K/AKT/mTOR signaling pathway. Moreover, the downregulation of targeted gene expression mediated by DNA methylation is an important regulatory mode to control protein expression. In the present review, methylation and tamoxifen are briefly introduced, followed by a focus on the effect of methylation on tamoxifen resistance and sensitivity. Finally, the clinical application of methylation for tamoxifen is described, including its use as a prognostic indicator. Finally, it is hypothesized that when methylation is used in combination with tamoxifen, it could recover the resistance of tamoxifen. [ABSTRACT FROM AUTHOR]

Established treatments for advanced hepatocellular carcinoma (HCC) with Child-Pugh cirrhosis B (CPB, moderate hepatic dysfunction) are lacking. A recently published randomized phase 2 study in CPB HCC investigating the safety and efficacy of namodenoson (25 mg BID), an A3 adenosine-receptor agonist vs. placebo, suggested a favorable safety profile and a positive efficacy signal in patients with HCC with a CPB score of 7 (CPB7). The present study reports a 61-year-old woman with CPB7 HCC who received namodenoson for over 6 years through this study and its open-label extension. Computed tomography scans demonstrated partial and complete responses after 7 weeks and 4 years of treatment, respectively. Low albumin levels (31 g/l) and elevated baseline levels of alanine transaminase and aspartate aminotransferase (68 U/l and 44 U/l, respectively) were reported. After 4 weeks of treatment, these levels normalized and were stable for over 6 years. No treatment-emergent adverse events were noted. At the time of reporting, the response is ongoing as manifested by imaging studies and liver function evaluation. [ABSTRACT FROM AUTHOR]

The prognostic significance of inflammation, immune response and nutritional status in patients with cancer is well-documented. The advanced lung cancer inflammation index (ALI) has emerged as a novel prognostic indicator, reflecting both inflammation and nutritional status. This study aimed to assess the prognostic relevance of preoperative ALI in patients with gastric cancer (GC). Data of 459 patients who underwent curative gastrectomy for GC between December 2013 and November 2017 at the Kanagawa Cancer Center (Yokohama, Japan) were retrospectively analyzed. Preoperative ALI was calculated from blood tests. Patients were divided into the high- and low-ALI groups. This study investigated the association between preoperative ALI, clinicopathological features, overall survival (OS) and relapse-free survival (RFS) after propensity-matched analysis. Comparative analysis revealed that patients in the low-ALI group tended to be older, were predominantly female, had lower body mass index and had a higher incidence of lymphatic invasion compared with those in the high-ALI group before propensity-matched analysis. Notably, the low-ALI group exhibited significantly reduced OS and RFS post-gastrectomy (85.5% vs. 93.8%, P=0.01; and 82.1% vs. 91.8%, P=0.02, respectively). Multivariate analysis identified low ALI as an independent prognostic factor for both OS and RFS. In conclusion, preoperative ALI could provide a valuable prognostic tool for patients with GC undergoing curative resection, offering insights into patient survival outcomes based on their inflammatory and nutritional status. [ABSTRACT FROM AUTHOR]

Midkine (MK) is a soluble cytokine, and its serum levels strongly correspond to protein expression levels in tumors. The present study aimed to clarify the clinicopathological and prognostic significance of serum MK (s-MK) in patients with hepatocellular carcinoma (HCC). Serum samples were obtained before surgery from 123 patients with HCC who had undergone surgery between January 2012 and December 2020. The receiver operating characteristic curve revealed that the best cut-off value for s-MK in differentiating HCC from healthy cases was 426 pg/ml. The clinicopathological variables and overall survival of patients were compared between the s-MK-positive group and s-MK-negative group. The sensitivity, specificity and accuracy of s-MK were 82.1, 97.4 and 88.0%, respectively. An s-MK-positive status was significantly associated with the number of tumors (≥2). The positivity rate of s-MK was significantly higher compared with that of α-fetoprotein and protein-induced by vitamin K absence-II. In total, only 28% of the patients were positive for s-MK. The s-MK-positive group showed significantly worse overall survival compared with the s-MK-negative group. Moreover, multivariate analysis revealed that an s-MK-positive status was independently associated with poor prognosis. s-MK was useful in detecting early HCC. The findings of this study indicated that the s-MK-positive status is associated with the number of tumors and can act as an independent prognostic risk factor. [ABSTRACT FROM AUTHOR]

Lung cancer is the most common cancer in the world due to its high incidence and recurrence. Genetic instability is one of the main factors leading to its occurrence, development and poor prognosis. Decreased xeroderma pigmentosum group C (XPC) expression notably enhances the stem cell properties of lung cancer cells and increases their proliferation and migration. Additionally, patients with lung cancer and low XPC expression had a poor prognosis. The purpose of the present study was to analyze the effect of XPC and IFN-γ on the clinical prognosis of patients with non-small cell lung cancer (NSCLC). Lung adenocarcinoma specimens were collected from a total of 140 patients with NSCLC. Additionally, from these 140 patients, 48 paracarcinoma tissue specimens were also collected, which were later used to construct tissue microarrays. The expression of XPC and IFN-γ in cancer tissues and in paraneoplastic tissues was detected using immunohistochemistry. The prognosis and overall survival of patients were determined through telephone follow-up. The results showed a positive correlation between expression of XPC and IFN-γ in NSCLC. Additionally, high expression of both markers was associated with a favorable prognosis in patients with NSCLC. The aforementioned findings suggest that the expression of XPC and IFN-γ has prognostic value in clinical practice and is expected to become a marker for clinical application. [ABSTRACT FROM AUTHOR]

In the present study, the efficacy and safety of a low dose of apatinib in the treatment of patients with advanced breast cancer (ABC) in a real-world setting were assessed, the impact of continuous anti-angiogenic therapy beyond progression was determined and the factors associated with efficacy were evaluated. A total of 63 patients with ABC who were treated with apatinib and for whom several lines of treatment had failed were retrospectively analyzed in Tangshan People's Hospital (Tangshan, China) between January 2016 and October 2022. Apatinib was administered orally combined with chemotherapy, endocrine therapy, targeted therapy or monotherapy at a dose of 250 mg per day. Apatinib administration was continued in certain patients beyond first progressive disease (PD), and these patients were defined as the continued anti-angiogenic treatment beyond first progression (CABF) group, while those who discontinued apatinib were defined as the non-CABF group. In the evaluation of the first efficacy, the objective response rate was 33.3%. A total of 26 patients continued to receive apatinib post-first PD and were allocated to the CABF group. The median overall survival (OS) time of the 63 patients was 16 months. Log-rank univariate analysis revealed that the OS time was significantly associated with molecular subtype (P=0.014), CABF (P=0.004), and the neutrophil-to-lymphocyte ratio (NLR) (P=0.011). Multivariate Cox regression analysis revealed that being in the non-CABF group and a high NLR were independent risk factors for lower OS time (P=0.017 and P=0.041, respectively). These results support the continued administration of low-dose apatinib beyond progression and the use of NLR as an easily accessible prognostic marker in patients with ABC treated with apatinib. [ABSTRACT FROM AUTHOR]

Metaplastic breast cancer (BC-Mp), which includes a range of epithelial and mixed epithelial-mesenchymal tumours, are rare malignancies with an unfavourable prognosis. The limited literature on BC-Mp focuses mainly on retrospective data for radically treated patients. Notably absent are studies dedicated to the palliative treatment of BC-Mp with distant metastases. The present retrospective study investigated treatment modalities and prognosis in a multi-centre cohort of 31 female participants diagnosed with distant metastatic BC-Mp, including 7 patients with de novo metastatic disease. The median age of the patients was 61 years (range, 33–87 years), with 38.7% presenting local lymph node involvement. Lungs were the most common site for the metastatic disease (61.3%). Median Ki-67 index was 50% (range, 35–70%), and 80.7% of cases were classified as grade 3. Human epidermal growth factor receptor 2 (HER2)+ and estrogen receptor+ were detected in 12.9 and 6.5% of cases, respectively. A total of 62.4% of patients received first-line palliative systemic treatment. The 1- and 2-year overall survival (OS) were 38.5 and 19.2%, respectively. Receiving ≥1 line of palliative treatment was significantly associated with improved OS (P<0.001). Factors such as age, Ki-67 index, HER2 or hormonal status, presence of specific epithelial or mesenchymal components, location of metastases or chemotherapy regimen type did not influence OS. The present study provided insights into the clinicopathological profile, systemic treatment experience, prognostic factors and OS data of BC-Mp with distant metastases, emphasizing the imperative for clinical trials in this population. [ABSTRACT FROM AUTHOR]

The aim of the present study was to detect CD177+ neutrophils in tumor tissues and analyze their association with the clinical characteristics and prognosis of patients with lung adenocarcinoma (LUAD). Immunohistochemistry was used to detect CD177+ neutrophils in tumors and adjacent tissues of 16 patients with LUAD who underwent curative surgical resection. A total of 120 patients with LUAD were recruited, and their clinical data were collected; survival follow-up was performed. CD177+ neutrophils in tumor tissues were detected via immunohistochemistry, and the association between CD177+ neutrophils and clinical characteristics was analyzed. The density of CD177+ neutrophils in tumor tissues and adjacent tissues of patients with LUAD was analyzed using t-test, and the association between CD177+ neutrophils and clinical characteristics was analyzed through the Chi-square test. Survival was calculated using the Kaplan-Meier survival rate curve. Finally, the association between these indicators and the survival of LUAD patients was evaluated using Cox regression analysis. CD177+ neutrophil infiltration was significantly higher in LUAD tumor tissues, and the high density of CD177+ neutrophils was associated with the clinical characteristics of TNM stage, tumor differentiation and poor progression-free and overall survival in LUAD. In conclusion, tumor-associated CD177+ neutrophils associated with malignant progression and poor prognosis may be independent and unfavorable prognostic biomarkers for LUAD. [ABSTRACT FROM AUTHOR]

Maspin is a serine protease inhibitor that is encoded by the human SERPINB5 gene. As a tumor inhibitor, it can inhibit the growth of tumor cells, increase adhesion between tumor cells and inhibit tumor angiogenesis. In the present study, a meta- and bioinformatics analysis was performed through the PubMed and China National Knowledge Infrastructure databases including entries added until up to March 20, 2023. It was found that compared with normal breast tissue, maspin expression was downregulated in breast cancer tissue. Maspin expression was negatively associated with lymph node metastasis. According to Kaplan-Meier plotter, it was found that lower maspin expression was negatively associated with the overall and distant metastasis-free survival rate of patients with estrogen receptor-positive, luminal A and grade 2 breast cancer. High expression of maspin was also positively associated with the relapse-free survival rate of patients of the luminal A subtype. Low maspin expression was positively associated with the post-progression and distant metastasis-free survival rate of the progesterone receptor-negative subtype. According to the GEPIA database, SERPINB5 mRNA expression was higher in normal than breast cancer tissues and negatively correlated with the TNM stage. High expression of maspin was also positively associated with the overall survival rate. In the UALCAN database, it was found that the mRNA and promoter methylation levels of SERPINB5 were higher in normal than in breast cancer tissues. These findings suggest that the expression of maspin may serve as a potential marker to indicate the occurrence, subsequent progression and even prognosis of breast cancer. [ABSTRACT FROM AUTHOR]