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Ovarian cancer's asymptomatic nature, high recurrence rate, and resistance to platinum‐based chemotherapy highlight the need to find and characterize new diagnostic and therapeutic targets. While prior studies have linked aberrant expression of fibroblast growth factor 8 (FGF8) to various cancer types, its precise role has remained elusive. Recently, we observed that FGF8 silencing reduces the cancer‐promoting properties of ovarian cancer cells, and thus, this study aimed to understand how FGF8 regulates the development of ovarian cancer. LC‐MS/MS‐based quantitative proteomics analysis identified 418 DEPs, and most of them were downregulated in FGF8‐silenced ovarian cancer cells. Many of these DEPs are associated with cancer progression and unfavorable prognosis. To decipher the biological significance of DEPs, bioinformatics analyses encompassing gene ontology, pathway analysis, protein‐protein interaction networks, and expression analysis of hub genes were carried out. Hub genes identified in the FGF8 protein network were upregulated in ovarian cancer compared to controls and were linked to poor prognosis. Subsequently, the expression of hub genes was correlated with patient survival and regulation of the tumor microenvironment. Conclusively, FGF8 and associated hub genes help in the progression of ovarian cancer, and their overexpression may lead to higher immune infiltration, poor prognosis, and poor survival. [ABSTRACT FROM AUTHOR]

Background. Coiled‐coil domain containing 25 (CCDC25) is a receptor for neutrophil extracellular trap (NET) DNA and is involved in various cancers, including CRC. This study aimed to investigate the regulatory role of CCDC25 in CRC using GWAS data, eQTL, transcriptomic profiles, and clinical information of CRC patients. Methods. From open‐source databases, GWAS summary data, eQTL expression profiles, and transcriptomic profiles, as well as clinical information were collected for CRC patients. Mendelian randomization (MR) was used to investigate the causal relationship between CCDC25 and CRC risk. The expression of CCDC25 and its associated differentially expressed genes (DEGs) were identified. We explored the relationship between CCDC25 expression and survival, biological functions, immune cell infiltration, immune checkpoint expression, and response to immunotherapy. Results. High CCDC25 expression reduces the risk of CRC. CCDC25 is downregulated in various cancers, particularly in CRC tumor tissues compared to normal tissues. Metabolic pathways are enriched in groups with high CCDC25 expression, while cancer‐related pathways are enriched in groups with low CCDC25 expression. High CCDC25 expression is also associated with increased infiltration of resting memory CD4+ T cells, elevated levels of most immune checkpoints, and an enhanced response to anti‐PD1 therapy. In addition, 95 DEGs were identified between high‐CCDC25 and low‐CCDC25 groups, and eight genes (FDFT1, ASAH1, ADAM9, CXCL14, SERPINA1, NAT1, EREG, and GSR) were identified as prognostic genes. Conclusion. CDC25 might serve as a candidate diagnostic and prognostic marker for CRC patients. [ABSTRACT FROM AUTHOR]

Extracellular vesicles play an important role in the progression of pancreatic adenocarcinoma (PAAD) through the transfer of proteins, mRNAs, and long noncoding RNAs (lncRNAs). However, the intricate interplay between extracellular vesicles‐related lncRNAs and the tumor microenvironment (TME) remains poorly elucidated. Consequently, our investigation aimed to delineate the association between extracellular vesicles‐related lncRNAs and the PAAD microenvironment. Initially, we identified differentially expressed lncRNAs (DELs) from The Cancer Genome Atlas (TCGA) and Genotype‐Tissue Expression (GTEx) project datasets. Subsequently, we validated the expression of these DELs within extracellular vesicles and assessed their prognostic implications in PAAD using the GSE133684 and TCGA datasets. Multiomics data were analyzed comprehensively, including genomic landscape, functional annotation, immune profiles, and therapeutic responses. Differential expression of selected lncRNAs in both cellular and exosomal fractions of PAAD was further confirmed through quantitative polymerase chain reaction (qPCR). Eight DELs were identified from TCGA and GTEx datasets, and two exosomal lncRNAs exhibited a significant correlation with overall survival, warranting further investigation. Specifically, elevated expression of LINC00996 correlated positively with immune infiltration and enhanced response to immunotherapy. Conversely, heightened expression of TRHED‐AS1 was associated with compromised immune cell infiltration and diminished responsiveness to immunotherapy. Our study establishes a compelling link between two extracellular vesicles‐related gene signatures, prognosis, and immune infiltration in PAAD. Notably, these signatures serve as robust prognostic indicators for PAAD patients, offering valuable insights for the strategic selection of immunotherapeutic interventions. [ABSTRACT FROM AUTHOR]

Background. Gastric cancer (GC) is the most common malignant tumor and ranks third in the world. LncRNA H19 (H19), one of the members of lncRNA, is overexpressed in various tumors. However, many undetermined molecular mechanisms by which H19 promotes GC progression still need to be further investigated. Methodology. A series of experiments was used to confirm the undetermined molecular mechanism including wound healing and transwell assays. Key Results. In this study, a significant upregulation of H19 expression was detected in GC cells and tissues. The poor overall survival was observed in GC patient with high H19 expression. Overexpression of H19 promoted the migration of GC cells, while knockdown of H19 significantly inhibited cell migration. Moreover, miR‐148a‐3p had a certain negative correlation with H19. Luciferase reporter assay confirmed that H19 could directly bind to miR‐148a‐3p. As expected, miR‐148a mimics inhibited cell migration and invasion induced by H19 overexpression. The above findings proved that H19 functions as a miRNA sponge and verified that miR‐148a‐3p is the H19‐associated miRNA in GC. We also confirmed that SOX‐12 expression was upregulated in GC patient's samples. SOX‐12 expression was positively correlated with expression of H19 and was able to directly bind to miR‐148a‐3p. Importantly, in vitro wound healing assay showed that knockout of SOX‐12 could reverse the promoting effect of H19 overexpression on cell migration. Conclusion. In conclusion, H19 has certain application value in the diagnosis and prognosis of GC. Specifically, H19 accelerates GCs to migration and metastasis by miR‐138a‐3p/SOX‐12 axis. [ABSTRACT FROM AUTHOR]

Background and Purpose. Occult breast cancer (OBC) is a rare condition. Due to the small number of patients in previous studies, the benefits of treatment with mastectomy are still discussed. This study aims to determine the clinicopathological characteristics, treatment, and prognosis of OBC presenting with locoregional lymph node metastasis (LNM). Materials and Methods. This study included patients registered in the national Danish Breast Cancer Group (DBCG) database between 2001 and 2015, with locoregional LNM as well as a bilateral negative mammography, ultrasonography, and physical examination of the breasts. Overall survival (OS) and invasive disease‐free survival (IDFS) were compared by treatment groups, ALND + RT (axillary lymph node dissection and radiotherapy) or ALND + MAST ± RT (axillary lymph node dissection, mastectomy with or without radiotherapy). Results. In total, 56 patients were included in the study, of which 37 were treated by ALND + RT, 16 by ALND + MAST ± RT, and the remaining three patients receiving different treatments. The median follow‐up for the 53 OBC patients sorted by treatment group was 12.2 years (interquartile range: 10.1 years; 15.3 years). There was no significant difference in OS or IDFS between the treatment groups, except for a subgroup of 46 (out of 53) patients without verified in situ lesions before treatment, where ALND + RT treatment showed an improved OS (log‐rank p = 0.05). Conclusion. Treating OBC patients with ALND and radiotherapy resulted in a similar outcome as treatment with ALND and mastectomy. This supports omission of mastectomy in favor of radiotherapy of the breast in these patients. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancers are known for their aggressive nature. This aggressiveness may be attributed to the presence of cancer stem cells (CSCs), which promote relapse, metastasis, and resistance to chemotherapy. Targeting CSCs is essential to reverse this aggressiveness in pancreatic malignancies. Literature highlights the association of PD‐L1 expression with CSCs in various cancers, suggesting immunotherapy as a promising therapeutic approach. This study is aimed at investigating the potential of immunotherapy in pancreatic cancers by examining its association with selected CSC marker expression. Method: A retrospective cohort study was conducted involving 56 patients with confirmed diagnoses of pancreatic cancers at Aga Khan University Hospital from January 2015 to October 2022. After exclusions, based on refusal to provide consent or incomplete follow‐up data, 38 patients were enrolled in the study. Immunohistochemistry was performed on formalin‐fixed paraffin‐embedded (FFPE) tumor tissue samples to assess the expression of CSC markers (CD133, CD44, and L1CAM) and immune checkpoint inhibitor marker (PD‐L1). Statistical analysis was employed to determine associations between marker expression, clinical factors, and overall survival. Results: The study revealed that 86.8% of pancreatic cancer cases exhibited positive PD‐L1 expression. Moreover, a significant association of PD‐L1 expression was observed with the presence of CD44 protein (p = 0.030), as well as with the overall survival of patients (p = 0.023). Conclusion: Our findings show a significant association of PD‐L1 with CD44 marker expression as well as patient survival. This research shows the potential to serve as the foundation for investigating the efficacy of immunotherapy in reducing CD44‐expressing CSCs in pancreatic cancer, potentially enhancing patient outcomes. [ABSTRACT FROM AUTHOR]

This study evaluated the effects of docetaxel and androgen receptor signaling inhibitors as second‐line treatments in patients with castration‐resistant prostate cancer after androgen receptor signaling inhibitors as first‐line treatment. This study retrospectively evaluated the clinical outcomes of second‐line treatment with docetaxel or androgen receptor signaling inhibitor in patients with castration‐resistant prostate cancer who received first‐line treatment with androgen receptor signaling inhibitors. Clinical backgrounds and outcomes were compared between docetaxel and androgen receptor signaling inhibitors as second‐line treatment. Of 59 patients, 21 (35.6%) and 38 (64.4%) received docetaxel and androgen receptor signaling inhibitors as second‐line treatment after first‐line treatment with androgen receptor signaling inhibitors, respectively. In the second‐line setting, the median progression‐free survival was longer with androgen receptor signaling inhibitor than with docetaxel (17 versus 6 months, P = 0.014). In the first‐line setting, the median progression‐free survival was longer with androgen receptor signaling inhibitors than with docetaxel (32 versus 25 months, P = 0.014); however, no significant difference was found in the overall survival. Multivariate analysis revealed that there was no significant association between second‐line treatment and survival, and first‐line treatment with abiraterone was identified as a prognostic factor for progression‐free survival. Subgroup analysis showed that the abiraterone–enzalutamide sequence was more effective than the other three sequences for progression‐free survival and overall survival. This study suggests that second‐line treatment with an androgen receptor signaling inhibitor for castration‐resistant prostate cancer after androgen receptor signaling inhibitors as first‐line treatment may be more beneficial, particularly with abiraterone as the upfront treatment. [ABSTRACT FROM AUTHOR]

Introduction. Triple‐negative breast cancer (TNBC) is a subgroup of breast cancer characterized by the absence of estrogen and the human epidermal 2 receptor and also a lack of targeted therapy options. Chemotherapy has so far been the only approved treatment option, and patients with metastatic cancer have a dismal prognosis with a median overall survival (OS) of approximately 14 months. Identification of druggable targets for metastatic TNBC is therefore of special interest. Methods. A systematic search was performed, to review the existing evidence on targeted therapies in metastatic TNBC. Results. A total of 37 phase 2/3 studies were identified, evaluating 29 different targeted agents. In this review, results on progression free survival (PFS) and OS are presented. Conclusion. In most of the studies included, no improvement was observed for neither PFS nor OS; however, a few studies did show improvement with targeted agents and have led to new treatment options in subgroups of patients. The antibody drug conjugate, sacituzumab govitecan, demonstrated superior PFS and OS in comparison to chemotherapy. Immunotherapy with checkpoint inhibitors such as atezolizumab and pembrolizumab is now recommended as a first‐line treatment option for patients with expression a PD‐L1 positive tumor. Finally, the poly adenosine diphosphate‐ribose polymerase (PARP) inhibitors talazoparib and olaparib are recommended, as first‐line treatment options in patients with metastatic breast cancer and a germline BRCA mutation, but an immune checkpoint inhibitor should be considered for the subset of these patients who are PD‐L1 positive. [ABSTRACT FROM AUTHOR]

Selective neck dissection (SND) is the treatment of choice in patients with oral squamous cell carcinomas (OSCCs) and clinically node‐negative necks (cN0). The treatment of patients with positive‐staged necks (cN+) includes SND as well as comprehensive neck dissection (CND). The clear benefit of one or the other remains under debate. We aim to address this lack of clarity by analysing patients with OSCC staged with clinically node‐positive necks, treated with either CND or SND using a level‐by‐level approach. This retrospective study included patients diagnosed with OSCC with clinically (cN+) and pathologically (pN+) positive cervical lymph nodes (LNs) with clear neck level categorization during the years 2010–2019. In total, 74 patients were analysed. Cox regression analysis found no significance for the type of ND being an independent risk factor, neither for overall survival (OS) nor for disease‐free survival (DFS). Regional recurrence of CND cases (5.77%) was comparable to SND cases (9.09%). For OS, extracapsular spread (ECS) and male sex were identified as independent risk factors with poorer outcome. pT‐stage and ECS were found to be independent risk factors for DFS. The results of this study suggest that both CND and SND may be viable treatment options for certain patients with OSCC pN+. [ABSTRACT FROM AUTHOR]

Heart transplantation from donors after circulatory death (DCD) has demonstrated increased primary graft dysfunction. Durable mechanical circulatory (MCS) recipients have slightly higher perioperative risk but excellent long‐term survival. We sought to determine if the use of DCD donors impacted outcomes for patients with MCS. The United Network for Organ Sharing database was queried from 2019 to 2023 for all adult recipients who underwent heart transplant with a durable left ventricular assist device (LVAD). Outcomes were compared for recipients of DBD and DCD donors. Kaplan–Meier analysis was used to compare survival. A total of 3449 recipients underwent heart transplant who met the study criteria. The number of DCD and DBD donors was 288 (8.4%) and 3161 (92.6%). There was no difference in the length of stay, postoperative dialysis, pacemaker, stroke rate, or in‐hospital mortality. Recipients with durable LVADs of DCD donors had a higher rate of treatment for rejection within the first year. Overall survival was not different between DBD and DCD donors (p = 0.153). Postoperative and survival outcomes for DCD donation remain similar between patients with and without MCS. These findings may help decrease waitlist time for patients with durable MCS. [ABSTRACT FROM AUTHOR]

Background: Invasive micropapillary carcinoma (IMPC) of the breast is commonly associated with a poor prognosis due to its high incidence of lymphovascular invasion and lymph node metastasis (LNM). Our study is aimed at investigating the prognostic significance of the expressions of E‐cadherin (E‐cad), N‐cadherin (N‐cad), CD44s, and β‐catenin (β‐cat). In addition, it is aimed at deciphering the consistency of these markers between the IMPC, the invasive breast carcinoma, no‐special type (IBC‐NST), and LNM components in the same IMPC cases. Methods: Sixty‐two IMPC cases with LNM from 1996 to 2018 were analyzed. Immunohistochemical staining was performed separately on the three regions for each patient. Statistical analyses included Kaplan‐Meier, Cox regression, and McNemar's statistical tests. Results: Loss of CD44 expression in IMPC, IBC‐NST, and LNM areas was associated with poor prognosis in overall survival (OS) (p = 0.010, p < 0.0005, p = 0.025). Loss of CD44 expression in the IBC‐NST, gain of N‐cad expression in the IMPC, and loss of β‐cat expression in the LNM areas were indicators of poor prognosis in disease‐free survival (DFS) (p = 0.005, p = 0.041, p = 0.009). Conclusion: Our evaluation of this rare subtype, focusing on the expression of key epithelial–mesenchymal transition (EMT) molecules, revealed that it shares characteristics with the IBC‐NST component within mixed tumors. Notably, contrary to expectations, a reduction in CD44 expression was found to adversely affect both OS and DFS. By conducting staining procedures simultaneously across three regions within the same patient, a novel approach has provided valuable insights into the mechanisms of EMT. [ABSTRACT FROM AUTHOR]

Cancer is a noncommunicable disease burden and the second‐leading cause of death worldwide. Novel medications and drug possibilities are sought everyday throughout the world in pursuit of cancer therapy. Colorectal cancer as one of the leading cancers across the globe can be treated effectively using TCM via decreasing the incidence and increasing the survival of patients. Gallic acid (GA) is an effective polyphenol used in TCM to treat several disorders including cancer. Our hypothesis was set to determine that GA possesses cytotoxic effects on CRC cells and that apoptosis and/or autophagy could be the rationale behind the mechanism. Therefore, in the current study, we investigated the cytotoxic effects of GA on human colorectal adenocarcinoma HT‐29 cells and the mechanisms of such effects. The IC50 for the cytotoxic effects of GA as evidenced by the MTT assay was 37.08 μg/mL. The outcomes indicated that GA can cause changes in MMP and result in the formation or accumulation of exogenous ROS at the IC50 dose. Consequently, the polyphenol can induce mitochondrial‐ or ER‐stress‐induced apoptosis and canonical autophagy other than contributing to the induction of ferroptosis in HT‐29 cells as evidenced by quantitative PCR and western blotting. Our results indicate that GA is an effective cytotoxic agent for the management of CRC at the preclinical level and is a valuable candidate for clinical trials. [ABSTRACT FROM AUTHOR]

Background: The role of BRAF in breast cancer pathogenesis is still unclear. To address this knowledge gap, this study is aimed at evaluating the impact of BRAF gene expression and copy number alterations (CNAs) on clinicopathologic characteristics and survival in patients with breast cancer. Methods: The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was obtained from the cBioPortal public domain. Tumoral BRAF mRNA expression and CNAs along with demographic and tumor data for patients with breast cancer were retrieved. The association of BRAF expression and CNAs with breast cancer clinicopathologic characteristics was analyzed. The impact of BRAF mRNA expression on the overall survival of patients was assessed using Kaplan–Meier survival analysis. Results: BRAF gene mRNA log intensity expression was positively correlated with tumor size and the Nottingham Prognostic Index (NPI) (p < 0.001). Alternatively, BRAF gene expression was negatively correlated with the age at diagnosis (p = 0.003). The average BRAF mRNA expression was significantly higher in premenopausal patients, patients with high tumor grade, hormone receptor–negative status, and non‐luminal tumors compared to postmenopausal patients, patients with low‐grade, hormone receptor–positive, and luminal disease. BRAF gain and high‐level amplification copy numbers were significantly associated with higher NPI scores and larger tumor sizes compared to neutral copy number status. Survival analysis revealed no discernible differences in overall survival for patients with low and high BRAF mRNA expression. Conclusion: High BRAF mRNA expression as well as the gain and high‐level amplification copy numbers were associated with advanced tumor characteristics and unfavorable prognostic factors in breast cancer. BRAF could be an appealing target for the treatment of premenopausal patients with hormone receptor–negative breast cancer. [ABSTRACT FROM AUTHOR]

Background. Distal malignant biliary obstruction (DMBO) can result in obstructive jaundice. Endoscopic ultrasound- (EUS-) guided biliary drainage (EUS-BD) has been an alternative for DMBO after failed ERCP. Aim. To compare the efficacy and safety between antegrade and transluminal approaches in patients with unresectable DMBO when ERCP failed. Methods. Patients with DMBO leading to obstructive jaundice after failed ERCP were enrolled in this study. We retrospectively evaluated the safety and efficacy between EUS-guided transluminal stenting (TLS group) and antegrade stenting (AGS group). Results. 82 patients were enrolled, of which 45 patients were in TLS group and 37 in AGS group. There were no statistical differences in the malignancy type, baseline common bile duct diameter, total bilirubin level, reason for EUS-BD, and history of biliary drainage between TLS and AGS groups. The technical success rate was statistically higher in TLS group than in AGS group (97.8 vs. 81.1%, P = 0.031). There were no statistical differences in clinical success rate, procedure-related adverse events, stent migration rate, stent dysfunction rate, reintervention rate, and overall patient survival time between TLS and AGS groups. The median time to stent dysfunction or patient death in TLS and AGS groups was 53 and 81 days, respectively (P = 0.017). Conclusions. Although AGS had a lower technical success rate than TLS, it was superior to TLS in stent patency in patients with DMBO. [ABSTRACT FROM AUTHOR]

Purpose. Breast cancer is a heterogeneous disease. Exploring new prognostic and therapeutic targets in patients with breast cancer is essential. This study investigated the expression of MET, ESR1, and ESR2 genes and their association with clinicopathologic characteristics and clinical outcomes in patients with breast cancer. Methods. The METABRIC dataset for breast cancer was obtained from the cBioPortal public domain. Gene expression data for MET, ESR1, and ESR2, as well as the putative copy number alterations (CNAs) for MET were retrieved. Results. The MET mRNA expression levels correlated inversely with the expression levels of ESR1 and positively with the expression levels of ESR2 (r = −0.379, p < 0.001 and r = 0.066, and p = 0.004 , respectively). The ESR1 mRNA expression was significantly different among MET CNAs groups p < 0.001 . Patients with high MET/ESR1 coexpression had favorable clinicopathologic tumor characteristics and prognosticators compared to low MET/ESR1 coexpression in terms of greater age at diagnosis, reduced Nottingham Prognostic Index, lower tumor grade, hormone receptor positivity, HER2-negative status, and luminal subtype p < 0.001 . In contrast, patients with high MET/ESR2 coexpression had unfavorable tumor features and advanced prognosticators compared to patients with low MET/ESR2 coexpression p < 0.001 . No significant difference in overall survival was observed based on the MET/ESR coexpression status. However, when data were stratified based on the treatment type (chemotherapy and hormonal therapy), survival was significantly different based on the coexpression status of MET/ESR. Conclusions. Findings from our study add to the growing evidence on the potential crosstalk between MET and estrogen receptors in breast cancer. The expression of the MET/ESR genes could be a novel prognosticator and calls for future studies to evaluate the impact of combinational treatment approaches with MET inhibitors and endocrine drugs in breast cancer. [ABSTRACT FROM AUTHOR]

Purpose. Recently, the association between ATRX and a more aggressive sarcoma phenotype has been shown. We performed a retrospective study of sarcomas from an individual institution to evaluate ATRX as a prognosticator in soft tissue sarcoma. Experimental Design. 128 sarcomas were collected from a single institution and stained for ATRX. The prognostic significance of these markers was evaluated in a smaller cohort of primary soft tissue sarcomas (n = 68). Kaplan–Meier curves were created for univariate analysis, and Cox regression was utilized for multivariate analysis. Results. High expression of ATRX was found to be a positive prognostic indicator for overall survival and metastasis-free survival in our group of soft tissue sarcomas both in univariate analysis and multivariate analysis (HR: 0.38 (0.17–0.85), P = 0.02 and HR: 0.49 (0.24–0.99), P = 0.05 , respectively). Conclusions. High expression of ATRX is a positive prognostic indicator of overall survival and metastasis-free survival in patients with STS. This is consistent with studies in osteosarcoma, which indicate possible mechanisms through which loss of ATRX leads to more aggressive phenotypes. Future prospective clinical studies are required to validate the prognostic significance of these findings. [ABSTRACT FROM AUTHOR]

Objective. Programmed cell death-1 (PD-1) inhibitors have shown potency for neoadjuvant therapy in several cancers, while their administration combined with concurrent chemoradiotherapy (CCRT) as a neoadjuvant therapy for locally advanced esophageal squamous-cell carcinoma (ESCC) is seldom reported. The current study aimed to investigate the pathological response, survival, and safety of neoadjuvant PD-1 inhibitor plus CCRT in locally advanced ESCC patients. Methods. Twenty-five locally advanced ESCC patients who underwent PD-1 inhibitor plus CCRT neoadjuvant therapy were retrospectively reviewed. Data regarding radiological response, pathological response, disease-free survival (DFS), overall survival (OS), and adverse events were retrieved. Results. Two (8.0%), 14 (56.0%), 9 (36.0%), and 0 (0.0%) patients had a clinical response of complete response, partial response, stable disease, and progressive disease after neoadjuvant therapy by radiological evaluations, respectively. Notably, 25 (100.0%) patients had successful tumor resections, 24 (96.0%) patients realized R0 resection, and 13 (52.0%) patients achieved pathological complete response (pCR) by pathological evaluations. Regarding survival profiles, the 1-year and 2-year accumulating DFS rates were 90.0% and 74.6%, respectively; then, the 1-year and 2-year accumulating OS rates were 95.5% and 90.4%, respectively. The top prevalent adverse events were fatigue (48.0%), nausea and vomiting (40.0%), leukopenia (36.0%), neutropenia (36.0%), and peripheral neuropathy (36.0%). In addition, grades 3-4 adverse events included peripheral neuropathy (12.0%), nausea and vomiting (4.0%), leukopenia (4.0%), neutropenia (4.0%), anemia (4.0%), and pruritus (4.0%). Conclusion. Neoadjuvant PD-1 inhibitor plus CCRT shows a good efficacy and acceptable tolerance for locally advanced ESCC treatment, but further large-scale study validation is needed. [ABSTRACT FROM AUTHOR]

Women around the world are most frequently afflicted with breast cancer, and it is one of the most frequent causes of cancer death in females. Breast cancer is usually classified according to biomarker status, triple‐negative breast cancer (TNBC) represents a distinct subtype characterized by immunohistochemical findings that denote negativity for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (Her-2) on cancer tissue. It is more common in younger women than in other subtypes. As an invasive breast cancer subtype with a unique drug-resistant phenotype and metastatic burden, it has limited treatment options, and patients have a poor prognosis with high rates of local, distant recurrence and mortality, and there is still a lack of standardized treatment protocols for TNBC. In this review, we delve into the current treatment strategies for TNBC and explore the potential for new approaches and targets in the future. This trial is registered with NCT03997123. [ABSTRACT FROM AUTHOR]

Aim. To compare the clinical characteristics of survival and nonsurvival patients with severe acute pancreatitis (SAP) and explore the risk of mortality in SAP patients. Methods. This was a single-center retrospective study performed in a severe acute pancreatitis diagnosis and treatment center. According to the outcome, SAP patients were divided into survival group and nonsurvival group. One-way ANOVA or independent t -test was used to compare the clinical characteristics of two groups of patients. Multivariate retrospective analysis was used to identify risk factors for mortality in SAP patients. Results. A total of 486 SAP patients were included in the study, and the 90-day mortality for SAP patients was 13.58%. The common etiologies of SAP are biliary tract diseases (69.75%) and hyperlipidemia (17.28%). The most common complications caused by SAP were organ failure (55.14%), ARDS (50.62%), AKI (30.45%), sepsis (27.16%), and abdominal fluid collection (27.57%). There were differences in age, complications, and medical intervention between the nonsurvival group and the survival group. The main causes of death were infection (46.97%), abdominal bleeding (28.79%), and organ failure (9.09%). The binary logistic regression analysis showed that there were significant differences in age, AKI, sepsis, abdominal hemorrhage, organ failure, laparotomy, creatinine, and APTT between the nonsurvival group and the survival group. Conclusion. Age, AKI, sepsis, abdominal hemorrhage, and organ failure are risk factors for mortality in SAP patients. SAP patients with high creatinine and prolonged APTT upon admission require doctors to be vigilant. The main cause of death in SAP patients is pancreatitis-related organ failure and secondary infection. [ABSTRACT FROM AUTHOR]

Background. In this research, programmed cell death protein 1 (PD-1) inhibitors, including toripalimab, sintilimab, and camrelizumab, were evaluated for the treatment of non-small-cell lung cancer (NSCLC). Methods. This retrospective research was conducted on patients with locally advanced and advanced NSCLC receiving various PD-1 inhibitors including toripalimab, sintilimab, and camrelizumab, between April 2019 and March 2023. Results. In total, the ORR and DCR of 167 patients included in this research were 40.72% (68/167) and 92.81% (155/167), respectively, while the statistical median PFS was 13.90 months (95% CI, 10.657–17.143), and the median OS was 30.10 months (95% CI, 22.142–38.058). Multifactorial analysis showed that two factors, line of treatment and history of smoking, had a statistically significant benefit on the patients' PFS benefit P < 0.05 , while the factor that had a statistically significant benefit on the patients' OS benefit was the presence of serious adverse events (AEs) during treatment. 83.83% and 24.55% of patients experienced any grade AEs and grade 3–5 AEs, respectively. Conclusions. In our research, therapy lines and history of smoking had influence on the efficacy of immunotherapy, while serious AEs during treatment were prognostic factors that affected the OS benefit of immunotherapy. Patients we studied did not die from treatment-related causes, and PD-1 inhibitors did not cause additional toxicity in elderly patients. However, further investigations and multicenter studies are needed. [ABSTRACT FROM AUTHOR]

Background. Ewing sarcoma (EwS) is a rare and highly malignant bone tumor primarily affecting children, adolescents, and young adults. The pelvis, trunk, and lower extremities are the most common sites, while EwS of the sacrum as a primary site is very rare, and only few studies focusing on this location are published. Due to the anatomical condition, local treatment is challenging in sacral malignancies. We analyzed factors that might influence the outcome of patients suffering from sacral EwS. Methods. We retrospectively analyzed data of the GPOH EURO-E.W.I.N.G 99 trial and the EWING 2008 trial, with a cohort of 124 patients with localized or metastatic sacral EwS. The study endpoints were overall survival (OS) and event-free survival (EFS). OS and EFS were calculated using the Kaplan–Meier method, and univariate comparisons were estimated using the log-rank test. Hazard ratios (HRs) with respective 95% confidence intervals (CIs) were estimated in a multivariable Cox regression model. Results. The presence of metastases (3y-EFS: 0.33 vs. 0.68; P < 0.001 ; HR = 3.4, 95% CI 1.7 to 6.6; 3y-OS: 0.48 vs. 0.85; P < 0.001 ; HR = 4.23, 95% CI 1.8 to 9.7), large tumor volume (≥200 ml) (3y-EFS: 0.36 vs. 0.69; P = 0.02 ; HR = 2.1, 95% CI 1.1 to 4.0; 3y-OS: 0.42 vs. 0.73; P = 0.04 ; HR = 2.1, 95% CI 1.03 to 4.5), and age ≥18 years (3y-EFS: 0.41 vs. 0.60; P = 0.02 ; HR = 2.6, 95% CI 1.3 to 5.2; 3y-OS: 0.294 vs. 0.59; P = 0.01 ; HR = 2.92, 95% CI 1.29 to 6.6) were revealed as adverse prognostic factors. Conclusion. Young age seems to positively influence patients' survival, especially in patients with primary metastatic disease. In this context, our results support other studies, stating that older age has a negative impact on survival. Tumor volume, metastases, and the type of local therapy modality have an impact on the outcome of sacral EwS. Level of evidence: Level 2. This trial is registered with NCT00020566 and NCT00987636. [ABSTRACT FROM AUTHOR]

Purpose. Glioblastoma is the most aggressive primary brain tumor, characterized by its distinctive intratumoral hypoxia. Sequential preoperative examinations using fluorine-18-fluoromisonidazole (18F-FMISO) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) could depict the degree of glucose metabolism with hypoxic condition. However, molecular mechanism of glucose metabolism under hypoxia in glioblastoma has been unclear. The aim of this study was to identify the key molecules of hypoxic glucose metabolism. Methods. Using surgically obtained specimens, gene expressions associated with glucose metabolism were analyzed in patients with glioblastoma (n = 33) who underwent preoperative 18F-FMISO and 18F-FDG PET to identify affected molecules according to hypoxic condition. Tumor in vivo metabolic activities were semiquantitatively evaluated by lesion-normal tissue ratio (LNR). Protein expression was confirmed by immunofluorescence staining. To evaluate prognostic value, relationship between gene expression and overall survival was explored in another independent nonoverlapping clinical cohort (n = 17) and validated by The Cancer Genome Atlas (TCGA) database (n = 167). Results. Among the genes involving glucose metabolic pathway, mRNA expression of glucose-6-phosphatase 3 (G6PC3) correlated with 18F-FDG LNR (P = 0.03). In addition, G6PC3 mRNA expression in 18F-FMISO high-accumulated glioblastomas was significantly higher than that in 18F-FMISO low-accumulated glioblastomas (P < 0.01). Protein expression of G6PC3 was consistent with mRNA expression, which was confirmed by immunofluorescence analysis. These findings indicated that the G6PC3 expression might be facilitated by hypoxic condition in glioblastomas. Next, we investigated the clinical relevance of G6PC3 in terms of prognosis. Among the glioblastoma patients who received gross total resection, mRNA expressions of G6PC3 in the patients with poor prognosis (less than 1-year survival) were significantly higher than that in the patients who survive more than 3 years. Moreover, high mRNA expression of G6PC3 was associated with poor overall survival in glioblastoma, as validated by TCGA database. Conclusion. G6PC3 was affluently expressed in glioblastoma tissues with coincidentally high 18F-FDG and 18F-FMISO accumulation. Further, it might work as a prognostic biomarker of glioblastoma. Therefore, G6PC3 is a potential key molecule of glucose metabolism under hypoxia in glioblastoma. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is a common malignant cancer in women with a low overall survival rate, and ferroptosis may be a potential new strategy for treatment. Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is a gene closely related to ferroptosis, yet the role of STEAP3 in OC has not yet been thoroughly investigated. Using biological information analysis, we first found that STEAP3 was highly expressed in OC, which was significantly associated with poor prognosis of patients and was an independent prognostic factor. Through cloning, scratch, and transwell experiments, we subsequently found that knockdown of STEAP3 significantly reduced the proliferation and migration ability of OC cells. Furthermore, we found that knockdown of STEAP3 induced ferroptosis in OC cells by detecting ferroptosis indicators. Mechanistically, we also found that knockdown of STEAP3 induced ferroptosis through the p53/SLC7A11 signaling pathway. Through tumorigenic experiments in nude mice, we finally verified that the knockdown of STEAP3 could inhibit tumor growth in vivo by promoting ferroptosis through the p53 pathway. Overall, our study identified a novel therapeutic target for ferroptosis in OC and explored its specific mechanism of action. [ABSTRACT FROM AUTHOR]

Lymphangiogenesis, an integral contributor to lymphatic metastasis, is a significant reason for the poor prognosis of cancer patients. Anti-lymphangiogenesis treatment is a promising novel therapeutic direction, especially for tumors resistant to conventional therapies. We confirmed the ectopic expression of lymphangiogenesis-related genes (LRGs) in lung adenocarcinoma (LUAD) cohorts based on the TCGA database. We constructed a prediction signature with 15 LRG prognostic signatures (F2RL1, LOXL2, MKI67, PTPRM, GPI, POSTN, INHA, LDHA, LINC00857, ITGA2, PECAM1, SOD3, GDF15, SIX1, and FGD5), and the overall survival (OS) was significantly different between the high- and low-risk groups (TCGA-training: p < 0.001 , TCGA-test: p = 0.02 , GSE30219: p < 0.001 , GSE37745: p = 0.002 , and GSE50081: p = 0.002). Moreover, the risk score was also associated with the PIK3CA and BRCA1 pathways. In the nomogram, the prognostic prediction of the risk score was better than that of clinicopathologic parameters in OS, including age, sex, stage, T stage, N stage, and M stage. In summary, we constructed and validated a 15-LRG signature, which may help predict the prognosis of LUAD and offer a possible direction for future research on downstream molecular mechanisms. [ABSTRACT FROM AUTHOR]

We present a case of recurrent ovarian cancer at the age of 75, gravida 1 para 0, with 18 years of disease-free survival. Chemotherapy brought a 10-month partial response status; to further improve the overall survival, the patient was evaluated using the AGO score (DESKTOP III trial, 2020), which was originally intended for cases immediately after the diagnosis of recurrence; the score has indicated a significant outcome; the patient went through a hepatosplenic metastatic site resection; and complete resection was achieved. Subsequently, the PARP inhibitor was introduced, which has led to 14 months of disease-free survival. Fifteen cases of late recurrence of epithelial ovarian cancer have been reported and are summarized at the end of this paper. [ABSTRACT FROM AUTHOR]

Background. Tesmin, a 60 kDa protein encoded by the metallothionein-like 5 (MTL5) gene, plays a vital role in spermatogenesis and oogenesis. Recent research has unveiled its potential involvement in malignancies, although its impact on HCC remains poorly understood. Methods. In this study, we sought to elucidate the clinical significance of tesmin in HCC patients. We investigated the relationship between tesmin expression and the prognosis of individuals with hepatocellular carcinoma (HCC), as well as its potential role in tumor proliferation and invasion. Immunohistochemistry (IHC) was employed to assess the expression of tesmin in HCC tissues. Chi-square tests were conducted to analyze the correlation between tesmin expression and various clinicopathological features among HCC patients. For survival analysis, we employed the Kaplan–Meier method and conducted Cox regression analyses. To investigate the functional role of tesmin, we utilized shRNA constructs for transfection-mediated knockdown. Proliferation was assessed using the CCK-8 assay, and invasive capability was determined through Matrigel Transwell assays. Results. IHC results indicated that tesmin expression was prominently observed in cancerous tissue. Notably, we observed a significant association between tesmin expression and tumor stage and invasion in HCC patients from both our medical center and TCGA dataset. Survival analysis further revealed that tesmin expression emerged as an independent prognostic factor for overall survival among individuals with HCC. Furthermore, cellular experiments demonstrated that knockdown of tesmin led to decreased proliferation and invasion of HCC cells. Conclusions. Our findings suggest that tesmin may serve as a novel prognostic marker for HCC, highlighting its potential as a target for further research into HCC treatment. Additionally, the functional experiments support the notion that tesmin may participate in promoting the proliferation and invasion of HCC cells, warranting further investigations into its mechanistic involvement in HCC progression. [ABSTRACT FROM AUTHOR]

Background. Meningeal solitary fibrous tumors (SFTs) are rare, malignant, mesenchymal tumors of the central nervous system. While surgical gross total resection is widely accepted as a positive prognostic factor for local control (LC), the role of postoperative radiotherapy (PORT) remains controversial. We sought to report our institutional experience with a particular focus on outcomes after PORT. Materials and Methods. In this single-center, retrospective cohort study, 20 patients with the primary diagnosis of histopathologically confirmed meningeal SFT were analyzed. Data on patient characteristics, imaging, treatment modalities, histopathology, and oncological outcomes were collected. LC and overall survival (OS) were assessed using the Kaplan–Meier estimator. Results. The median follow-up time was 95.8 months. After surgery only, 9 out of 11 patients (81.8%) developed a local recurrence while, after surgery and PORT, 3 out of 9 patients (33.33%) showed local failure. The 5- and 10-year LC rates were 50.5% and 40.4% in the surgery-only group and 80% at both time points in the surgery with the PORT group. In the surgery-only group, 4 out of 11 patients (36.4%) died, and 4 out of 9 patients (44.4%) died in the surgery and PORT group. OS rates after 5 and 10 years were 88.9% and 66.7% in the surgery-only group and 88.9% and 76.2% in the surgery with PORT group. Conclusions. Our findings suggest that PORT may improve LC in patients with meningeal SFT. The low incidence of meningeal SFT impedes prospective studies and requires further international collaborative efforts to exploit retrospective datasets and molecular analysis to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background. Growing evidence has revealed that m6A modification of long noncoding RNAs (lncRNAs) dynamically controls tumor stemness and tumorigenesis-related processes. However, the prognostic significance of m6A-related lncRNAs and their associations with stemness in low-grade glioma (LGG) remain to be clarified. Methods. A multicenter transcriptome analysis of lncRNA expression in 1,247 LGG samples was performed in this study. The stemness landscape of LGG tumors was presented and associations with clinical features were revealed. The m6A-related lncRNAs were identified between stemness groups and were further prioritized via least absolute shrinkage and selection operator Cox regression analysis. A risk score model based on m6A-related lncRNAs was constructed and validated in external LGG datasets. Results. Based on the expression of LINC02984, PFKP-DT, and CRNDE, a risk model and nomogram were constructed; they successfully predicted the survival of patients and were extended to external datasets. Significant correlations were observed between the risk score and tumor stemness. Moreover, patients in different risk groups exhibited distinct tumor immune microenvironments and immune signatures. We finally provided several potential compounds suitable for specific risk groups, which may aid in LGG treatment. Conclusions. This novel signature presents noteworthy value in the prediction of prognosis and stemness status for LGG patients and will foster future research on the development of clinical regimens. [ABSTRACT FROM AUTHOR]

Aim. To examine the clinical management of metaplastic breast cancer (MeBC), particularly the role of chemotherapy. Methods. This retrospective study included patients with MeBC (n = 73) from a tertiary breast cancer center: the "Centre des Maladies du Sein of the CHU de Québec–Université Laval." The specimens were reviewed by two pathologists. Patient and tumor characteristics, systemic therapy (neoadjuvant and adjuvant), disease-free survival (DFS), and overall survival (OS) were recorded. Results. The median follow-up was 57.2 months. The mean tumor size was 39.5 ± 32.1 (range, 1–200) mm. Most were in grade 3 (75.3%), without evidence of clinical nodal involvement (75.3%), and triple-negative (79.5%). Chemotherapy was given to 49 (67.1%) patients. Thirty-seven patients (50.7%) underwent a mastectomy, and 22/37 (59.5%) received radiotherapy. Adjuvant chemotherapy was given to 36 patients (49.3%), and nine (12.3%) patients were treated with neoadjuvant chemotherapy. The 5-year OS and DFS rates were 60.2% and 66.8%. Among the nine patients who received neoadjuvant chemotherapy, three (33.3%) achieved a partial response, three (33.3%) had stable disease, and three (33.3%) had disease progression. The use of chemotherapy, especially in the adjuvant setting, had a significant positive effect on 5-year OS (P = 0.003) and 5-year DFS (P = 0.004). Nodal involvement was associated with worse OS (P = 0.049) but similar DFS (P = 0.157). Lumpectomy was associated with better 5-year OS (P < 0.0001) and DFS (P = 0.0002) compared with mastectomy. Conclusion. MeBC represents a rare heterogeneous group of malignancies with poor prognosis. Adjuvant chemotherapy was associated with improved OS and DFS. Patients should be carefully selected for neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) has emerged as an extremely destructive malignancy, causing significant harm to female patients and society at large. Proteomic research holds great promise for early diagnosis and treatment of diseases, and the integration of proteomics with genomics can offer valuable assistance in the early diagnosis, treatment, and improved prognosis of BC patients. In this study, we downloaded breast cancer protein expression data from The Cancer Genome Atlas (TCGA) and combined proteomics with genomics to construct a proteomic-based prognostic model for BC. This model consists of nine proteins (HEREGULIN, IDO, PEA15, MERIT40_pS29, CIITA, AKT2, CD171 DVL3, and CABL9). The accuracy of the model in predicting the survival prognosis of BC patients was further validated through risk curve analysis, survival curve analysis, and independent prognostic analysis. We further confirmed the impact of differential expression of these nine key proteins on overall survival in BC patients, and the differential expression of the key proteins and their encoding genes was validated using immunohistochemical staining. Enrichment analysis revealed functional associations primarily related to PPAR signaling pathway, steroid hormone metabolism, chemokine signaling pathway, DNA conformation changes, immunoglobulin production, and immunoglobulin complex in the high- and low-risk groups. Immune infiltration analysis revealed differential expression of immune cells between the high- and low-risk groups, providing a theoretical basis for subsequent immunotherapy. The model constructed in this study can predict the survival of BC patients, and the identified key proteins may serve as biomarkers to aid in the early diagnosis of BC. Enrichment analysis and immune infiltration analysis provide a necessary theoretical basis for further exploration of the molecular mechanisms and subsequent immunotherapy. [ABSTRACT FROM AUTHOR]

Introduction. There has been increased interest in HER2-low breast tumors recently, as these tumors may have distinct clinical and molecular characteristics compared to HER2-negative and HER2-positive tumors. A new nomenclature has been proposed for HER2 1+ and HER2 2+ tumors that are confirmed negative according to fluorescence in situ hybridization (FISH). These tumors are now referred to as HER2-low, and it is thought that they may represent a distinct subtype of breast cancer that warrants further investigation. In this study, we aimed to evaluate the clinicopathological characteristics and prognostic impact of this particular subtype in a North-African context where HER2-low breast cancer is a relatively understudied subtype, particularly in non-Western populations. Methods. We conducted a retrospective cohort study on 1955 breast tumors in Moroccan patients over 10 years, collected at the Pathology Department of Ibn Rochd University Hospital in Casablanca and at the pathology department of Hassan II University Hospital in Fes. We elaborated on their complete immunohistochemical profile based on the main breast cancer biomarkers: Ki-67, HER2, estrogen, and progesterone receptors. Their overall survival and disease free survival data were also retrieved from their respective records. Results. Out of 1955 BC patients, 49.3% were classified as HER2-low; of which 80.7% and 19.2% were hormone receptors positive and negative, respectively. The clinicopathologic features indicate that HER2-low subtype tumors behave much more like HER2-positive than HER2-negative tumors. The survival analysis showed that the HER2-low subtype-belonging patients present significantly the poorest prognosis in disease-free survival (p = 0.003) in comparison with HER2-negative ones. When considering the hormonal status, hormonal-dependent tumors show a significant difference according to HER2 subtypes in disease-free survival (p < 0.001). Yet no significant difference was shown among hormonal negative tumors. Moreover, patients with hormonal positive tumors and simultaneously belonging to the HER2-low subgroup present a significantly good prognosis in overall survival compared to the ones with hormonal negative tumors (p = 0.008). Conclusion. Our study has shown that the HER2-low phenotype is common among hormone-positive patients. The clinicopathological features and prognostic data indicate that the hormonal receptors effect and HER2 heterogeneity are crucial factors to consider. It is important to note that this particular subgroup is different from the HER2-negative one and should not be treated in the same way. Therefore, this study offers a new perspective in the management of HER2-low patients and can serve as a basis for future prospective analyses. [ABSTRACT FROM AUTHOR]

Aims. The available research on the association between estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), ER−/PR+ status, and the occurrence of lung cancer subsequent to breast cancer in patients (referred to as BC-LuC) had been limited. Consequently, there is a need to examine whether ER, PR, HER2, and ER−/PR+ have independent correlations with the risk and outcomes of BC-LuC, while appropriately adjusting for other potential covariates. Methods. The present study employed a cohort design and utilized data from the Surveillance, Epidemiology, and End Results (SEER) program spanning from 2010 to 2015. The study population consisted of 683,336 individuals who were diagnosed with breast cancer (referred to as BC). Various covariates were assessed at baseline, including age, sex, race, marital status, CS tumor size, laterality, radiation, chemotherapy, months from diagnosis to treatment, breast subtype, AJCC 7th edition (2010–2015), and combined summary stage (2004+). The primary objective of this study was to investigate the association between ER, PR, HER2, ER−/PR+ status, and the risk of developing BC-LuC. Logistic regression analysis was employed to assess this association. Furthermore, multivariable Cox regression analyses were conducted to calculate adjusted hazard ratios (HRs) along with their respective 95% confidence intervals (CIs). Kaplan–Meier plots and log-rank tests were utilized to estimate the outcomes, specifically overall survival (OS), disease-specific survival (DSS), and metastasis. Results. The average age of 198,972 selected participants was 59.8 ± 13.1 years, and about 99.3% of them were female. Result of fully adjusted binary logistic regression showed PR+ and HER2+ were positively associated with lower risk BC-LuC after adjusting confounders (ORs = 0.84, 95% CI: 0.73–0.96, p = 0.011 and ORs = 0.83, 95% CI: 0.72–0.96, p = 0.012, respectively). ER+ and ER−/PR+ were detected no significant relationship with BC-LuC (ORs = 1.03, 95% CI: 0.87–1.22, p = 0.718 and ORs = 1.02, 95% CI: 0.61–1.72, p = 0.936, respectively). In subgroups analyses, the results remain stable. Multivariable Cox regression showed that BC-LuC patients with ER and PR were significantly associated with OS and DSS. However, ER, PR, HER2, and ER−/PR+ were significantly associated with OS and DSS in breast cancer patients. The relationship between ER, PR, HER2, and ER−/PR+ and metastasis in breast cancer patients was different. Conclusion. The results of this study indicated a potential correlation between PR- and HER2- status and a risk of developing BC-LuC. Furthermore, it appears that the prognosis of BC-LuC may be influenced by the presence of ER+ and PR+. Therefore, additional research is warranted to fully investigate and validate this association. [ABSTRACT FROM AUTHOR]

This review summarizes the correlation between diabetes mellitus (DM) and gastric cancer (GC) from the perspectives of epidemiology, drug use, and potential mechanisms. The association between DM and GC is inconclusive, and the positive direction of the association reported in most published meta-analyses suggests that DM may be an independent risk factor for GC. Many clinical investigations have shown that people with DM and GC who undergo gastrectomy may have better glycemic control. The potential link between DM and GC may involve the interaction of multiple common risk factors, such as obesity, hyperglycemia and hyperinsulinemia, H. pylori infection, and the use of metformin. Although in vitro and in vivo data support that H. pylori infection status and metformin can influence GC risk in DM patients, there are conflicting results. Patient survival outcomes are influenced by multiple factors, so further research is needed to identify the patients who may benefit. [ABSTRACT FROM AUTHOR]

Aim. The Hyper-CVAD regimen has shown promising results for adult patients with acute lymphoblastic leukemia (ALL), as designed by the MD Anderson Cancer Center (MDACC). This treatment has resulted in a complete remission rate of 92% and a 5-year overall survival of 38%. However, given the diversity of patient demographics and institutional methods, outcomes may differ between various institutions. This study will compare the outcome of adult ALL patients treated with the Hyper-CVAD regimen in Iran with those obtained in the original series presented at the MDACC. Patients and Method. In this retrospective study, we evaluated the 2-year leukemia-free survival (LFS) and the 2-year overall survival (OS) of 70 ALL patients treated between 2014 and 2019 in the Seyed Al-Shohada Hospital in Isfahan, Iran. Results. In total, 59 ALL patients (84.28%) achieved complete remission (CR). The CR rate had statistical differences by bone marrow transplantation (BMT) and WBC count. The 2-year LFS and OS were 40% and 42%, respectively. There were significant differences in LFS and OS by BMT, myeloid marker, and WBC count. Conclusion. The outcome of the traditional Hyper-CVAD regimen in treating adult ALL was not satisfying. More efficient therapies should be applied for the treatment of adult ALL. [ABSTRACT FROM AUTHOR]

Introduction and Aim. Sentinel lymph node (SLN) mapping has been developed as an alternative to complete lymphadenectomy for the surgical staging of early-stage, uterine-confined endometrial cancer to reduce the morbidity of lymphadenectomy and has been demonstrated as a safe and feasible alternative. We compare the surgical and oncological outcomes between SLN mapping with routine lymphadenectomy in the surgical staging of early-stage endometrial cancer in our centre. Methods. A retrospective single-centre cohort study of patients with early-stage endometrioid endometrial cancer undergoing staging surgery (total hysterectomy, bilateral salpingo-oophorectomy with/without pelvic lymph node, and/or para-aortic lymph node dissection (PLND)) with either SLN mapping or routine lymphadenectomy between July 2017 and December 2018. Results. 203 cases with clinical and radiological International Federation of Gynaecology and Obstetrics (FIGO) stage I endometrioid endometrial cancer were included, out of which 109 cases underwent SLN mapping and 94 cases complete lymphadenectomy. Compared to the PLND group, the SLN group had shorter operative time (129 vs. 162 minutes), less blood loss (100 vs. 300 ml), and decreased length of postoperative hospital stay (3 vs. 4 days) (p < 0.001). The lymph node metastases detection rate was 4.6% and 7.4% for the SLN and PLND groups, respectively (p = 0.389). With a median follow-up of 14 months for the SLN and 15 months for the PLND group, the disease-free (DFS) and overall survival (OS) were comparable for both at 13 months (p = 0.538 and p = 0.333 , respectively). Conclusion. SLN mapping has been shown to be an acceptable alternative to routine lymphadenectomy in the surgical staging of early-stage endometrial cancer in our centre, with a comparable lymph node metastases detection rate, DFS and OS, and reduction in operative morbidity. Our results with SLN mapping reproduce comparable outcomes to those reported in the literature. [ABSTRACT FROM AUTHOR]

Introduction. Prephase treatment (PP) is recommended in diffuse large B-cell lymphomas (DLBCL) to decrease therapy-related toxicities and to avoid tumour lysis syndrome. Data in the real world are limited, and no study has evaluated the impact on overall survival. We aimed to evaluate overall survival (OS), progression-free survival (PFS), and grade III-IV toxicities during the first cycle according to PP. Methods and Materials. All DLBCL diagnosed between 2014 and 2017 and aged between 18 and 80 years were identified by the Poitou-Charentes General Cancer Registry (France). PP was defined as any treatment prior to first-line, excluding anthracycline and/or Rituximab. We performed propensity score matching (PSM) to control characteristics at diagnosis, reduce bias, and approximate a randomized trial. Results. Three hundred and forty patients received first-line treatment in 17 hospital centers: 126 (37%) with prephase and 214 (63%) without prephase (NPP). After PSM, 97 patients remained in each group without significant difference in characteristics at diagnosis; matched PP patients had a 2-year OS of 71% (vs. 77%, P = 0.32), a 2-year PFS of 61% (vs. 74%, P = 0.12), and 26% grade III-IV toxicities (vs. 27%, P = 0.75). No tumour lysis syndrome was reported. PP nonsignificantly decreases grade III-IV toxicities for patients with high tumour load (P = 0.82) or elderly patients (P = 0.81). Conclusion. PP treatment does not affect survival nor does it reduce therapy-related toxicities even for patients with high tumour load or elderly patients. Further studies are needed to evaluate the efficacy and safety of PP. [ABSTRACT FROM AUTHOR]

Background. CDK 4/6 inhibitors with hormonal therapy are the standard first-line therapy in metastatic hormonal receptors (HR)-positive and HER2-negative breast cancer. This study aims to assess the impact of neutropenia with 1st cycle, dose reduction, HER2-low status, and other clinicopathological factors on survival outcomes with the first-line palbociclib and hormonal therapy. Patients and Methods. In this retrospective study, we recruited patients with metastatic HR-positive and HER2-negative breast cancer. Neutropenia with 1st cycle, palbociclib dose reduction in addition to different clinicopathological and survival data were checked in patients' medical records. Survival outcomes were compared according to the abovementioned factors. Results. We recruited 150 patients who received first-line palbociclib with hormonal therapy. 86% of patients developed 1st cycle neutropenia which was more common in patients with high Ki67. Dose reduction was recorded in 46.7% of patients and it was more common in patients with higher Allred scores (scores 7–8). The median progression-free survival (PFS) of the study group was 22 months. No significant difference was observed in PFS according to the 1st cycle of neutropenia or grade of neutropenia. Similarly, no difference in PFS according to palbociclib dose reduction and HER2 low status was observed. Only the Allred score and having a single site of metastasis had an independent significant relation with PFS. The median overall survival (OS) of the study group was 39 months. No significant difference was observed in OS according to the 1st cycle neutropenia, grade of neutropenia, palbociclib dose reduction, and HER2-low status. Only the Allred score and having a single site of metastasis had an independent significant relation with OS. In addition, no difference was observed in PFS and OS according to ECOG PS (2 vs. 0-1) or menopausal status. Conclusion. No significant impact of the 1st cycle neutropenia, dose reduction, having ECOG PS2, menopausal status, or HER2 low status on survival outcome was observed. Survival outcome was significantly better in patients with single metastatic sites and higher ER-Allred scores. [ABSTRACT FROM AUTHOR]

Canine mammary tumors (CMTs) are the most diagnosed neoplasms in dogs; however, there are few studies analyzing the influence of epidemiological, clinicopathological, and histopathological data on cancer-specific survival (CSS), disease-free interval (DFI), and overall survival (OS) in a large cohort. To contribute to the understanding of the biological behavior of this neoplasm, 385 cases were analyzed, 89% malignant, 4% benign, and 7% non-neoplastic lesions. Among the dogs diagnosed with malignant neoplasms, 86% had early clinical stages (I–III), while 14% had regional or distant metastasis at the time of diagnosis. Carcinoma in a mixed tumor was the most frequent histological type with 44% of the cases and had the best prognosis. Analyzed factors such as the presence of pseudocyesis, previous history of the disease, advanced clinical stage (IV-V), and presence of ulceration obtained significant results for CSS, DFI, and OS through univariate analysis and had a negative impact on the survival of the patients. Multivariate analysis showed that histological grading and age proved to be the best independent parameters for the prognostic evaluation of CSS and DFI in this study. These factors were also significant in the overall survival analysis. Therefore, these parameters should be considered valuable risk and prognostic factors for CMTs. [ABSTRACT FROM AUTHOR]

Objective. To clarify the relationship between preoperative platelet count/(lymphocyte count × prealbumin count) ratio (PLPR) and the prognosis of patients with gastric cancer undergoing a radical operation, combined with Tumor Node Metastasis (TNM) staging, a scoring system was established to guide clinical application. Methods. The clinical data of 238 patients receiving radical operations for gastric cancer were retrospectively analyzed. According to the area under the Receiver operating characteristic curve, the predictive value of the preoperative PLPR for the 5-year overall survival (OS) of gastric cancer was determined, and the best cut-off value of the ratio was corresponding to the maximum value of Yoden index. Chi-squared test was applied to analyze the correlation between the ratio and clinicopathological features. Kaplan–Meier curve was applied to analyze the influence of this ratio on 5-year OS. The Cox regression model was applied to analyze the hazards affecting the long-term survival of patients. The nomogram model was used to predict the long-term survival rate. Results. The optimal cut-off point of preoperative PLPR ratio was 7.46, and the patients were segmented into two sets: one set of ratio <7.46 and another set of ratio ≥7.46. The ratio was correlated with the size of the tumor, T stage, N stage, total stage, vascular cancer thrombus, and nerve invasion. In stage I–III patients, the prognosis was better in the low-ratio set than in the high-ratio set (P < 0.001), subgroup analysis indicated the prognosis was obviously better in the low-ratio set than in the high-ratio set in stage II and III patients (P < 0.05 and P < 0.001), but there was no difference in stage I patients (P > 0.05). Age, T stage, N stage, total TNM stage, tumor size, vascular tumor thrombus, nerve invasion, preoperative neutrophil count/lymphocyte count (NLR; reference value 3.68), preoperative PLPR (reference value 7.46), preoperative platelet count/lymphocyte count (PLR; reference value 159.56), and preoperative platelet count × NLR (SII; reference value 915.48) were related to patient prognosis (P < 0.05); meanwhile age, total TNM stage, preoperative PLPR (reference value 7.46), preoperative PLR (reference value 159.56), and preoperative SII (reference value 915.48) were independent hazards for prognosis (P < 0.05). Five independent risk factors were analyzed by nomogram model to predict the 5-year OS of patients who underwent a radical operation for carcinoma of the stomach. Conclusion. Preoperative PLPR ratio (reference value 7.46) is an independent risk factor for long-term prognosis in patients undergoing a radical operation for gastric cancer. The nomogram scoring system established by postoperative TNM staging combined with this ratio and age, PLR, and SII can better forecast the survival of patients who underwent radical operation for carcinoma of the stomach. [ABSTRACT FROM AUTHOR]

Background. Female cancers cover common breast cancers, relatively common endometrial, ovarian, and cervical cancers and rare vulvar cancer. Survival in these cancers is known to be relatively good compared to all cancers but long-term studies for these cancers are rare, and to fill the gap, here, we generate survival data through 50 years. Materials and Methods. We applied generalized additive models to data from the NORDCAN database and analyzed 1- and 5-year relative survival for these cancers in Denmark (DK), Finland (FI), Norway (NO), and Sweden (SE) over half a century (1971–2020). Conditional 5/1-year survival for patients who survived the 1st year after diagnosis and annual survival changes was also estimated. Results. In 2016–20, 5-year survival was best for breast cancer reaching 92.3% (in SE), followed by endometrial cancer at 86.1% (SE) and cervical cancer at 75.6% (NO). Improvement in 5-year survival over the 50 years was the largest for ovarian cancer (20% units), finally reaching 52.9% (SE). For vulvar cancer, the final survival was between 70 and 73%. The best 5-year survival rate in 2016–20 was recorded for SE in breast, endometrial, and ovarian cancers; NO showed the highest rate for cervical and DK for vulvar cancers. DK had the lowest survival for breast and ovarian cancers, and FI, for the other cancers. Conclusions. The overall survival development appeared to consist of continuous improvements, most likely because of novel treatment and imaging techniques as well as overall organization of patient care. The large survival improvement for ovarian cancer was probably achieved by a surgical focus on tumors spread in the peritoneal cavity. For cervical and vulvar cancers, the high early mortality requires attention and could be helped by raising increasing public awareness of early symptoms in these cancers and developing pathways for fast initiation of treatment. [ABSTRACT FROM AUTHOR]

Objective. Metformin is a common antidiabetic drug that has been reported to serve as an anticancer agent in combination with other therapies. But the effect of the addition of metformin on the survival of non-small cell lung cancer (NSCLC) patients undergoing chemotherapy is still controversial. We conducted this systematic review to evaluate the survival effect of metformin added to chemotherapy in NSCLC patients. Methods. Electronic literature search was performed in the PubMed, Embase, and Web of Science databases from their inception up to April 2023. The study region, study design, histological subtype of the NSCLC, tumor stage, treatment strategy, sample size, follow-up duration, diabetes status, and HR of OS or PFS of the included studies were extracted. The quality was assessed through Cochrane collaboration's tool for RCT and the Newcastle–Ottawa scale (NOS) for observational studies, respectively. Results and conclusions. Eleven studies with a total of 4606 patients were finally included. Five RCTs showed a high risk of bias due to the open-label nature while six retrospective studies were of high quality. Two studies of NSCLC patients with diabetes reported significant benefits in overall survival from metformin addition, while one study of patients without diabetes reported a negative effect on the survival of metformin addition. The survival impact of metformin added to chemotherapy on unresectable NSCLC patients remains inconclusive. The survival benefit might be more prominent in patients with diabetes, awaiting further evidence. [ABSTRACT FROM AUTHOR]

Purpose. Paclitaxel and carboplatin are novel anticancer drugs that have emerged in recent years, while there is still a lack of clinical consensus on these two drugs. The study conducted a meta-analysis and systematic review to analyze the efficacy and safety of paclitaxel and carboplatin for platinum-sensitive ovarian cancer. Methods. A systematic search was carried out in three databases of the Cochrane Library, Embase, and PubMed from the inception of each database to March 2021, and defined the progression-free survival and overall survival as the primary outcomes. Data analysis was performed using STATA 15.1. Results. Altogether, five randomized controlled trials (RCTs) were included in the meta-analysis, involving 2,740 patients, including 1317 in the CD (carboplatin doxorubicin) group and 1423 in the CP (carboplatin plus paclitaxel) group. It was found that pooled OS demonstrated no significant differences between the CD group and CP group (HR = 1.02, 95% CI = 0.89–1.18, P = 0.340), and the differences were not statistically significant in progression-free survival (HR = 0.84, 95% CI = 0.71–0.99, P = 0.140), thrombocytopenia (OR = 0.23, 95% CI = 0.09−0.58, P = 0.775), and grade II alopecia between the two groups (OR = 9.41, 95% CI = 6.57–13.47, P = 0.215). Conclusion. Current evidence suggests that paclitaxel and carboplatin do not produce more satisfactory results with respect to overall survival and reduction of side effects in treating platinum-sensitive ovarian cancer, and further studies are needed. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 11 (FGF11) accelerates tumor proliferation in a variety of cancer types. This study aimed to examine the link between FGF11 and the prognosis of lung adenocarcinoma. FGF11 was searched in the Tumor Cancer Genome Atlas (TCGA) and ImmProt databases. The link between FGF11 and lung cancer clinical data was investigated using TCGA and Kaplan–Meier (KM)-plotter databases, and we developed a prediction model. Putative mechanisms of action were investigated using Gene Ontology (GO) and KEGG enrichment analyses. The GeneMANIA and STRING databases were used to search for genes that interact with FGF11, and the Tumor Immune Estimation Resource (TIMER) database was used to discover connections between FGF11 and immune cells, as well as any correlations with immune-related genes. We found that FGF11 expression was higher in the lung adenocarcinoma tissue than in the paracancerous tissue, and patients with high FGF11 expression had a lower overall survival, progression-free survival, and disease specific survival rate than those with low FGF11 expression. The expression of FGF11 was inversely linked to six types of infiltrating immune cells in the TIMER database and was associated with EGFR, VEGFA, BRAF, and MET expressions. The FGF11 gene is negatively correlated with the expression of most immune cells, mainly with various functional T cells including Th1, Th1-like, Treg, and Resting Treg characterization genes. These results indicate that FGF11 has the potential to be a new lung adenocarcinoma biomarker. It increases tumor cell immune escape by boosting T cell exhaustion in the tumor microenvironment, contributing to the poor prognosis of the patients with lung adenocarcinoma. These results provide incentive to further research FGF11 as a possible biomarker and drug target for patients with lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Purpose. To identify the survival and prognostic factors for cardiac amyloidosis (CA) in Chinese patients. Methods. This was a prospective cohort study of 72 patients diagnosed with CA and admitted to the PLA General Hospital between November 2017 and April 2021. Demographic, clinical, laboratory, electrocardiographic, conventional ultrasound, endocardial LS during LV systole (LV ENDO LSsys), and myocardial strain data were recorded. Survival was assessed. All-cause mortality was the endpoint. Follow-up was censored on September 30, 2021. Results. The mean follow-up was 17.1 ± 12.9 months. Among the 72 patients, 39 died, 23 survived, and 10 were lost to follow-up. Mean survival for all patients was 24.7 ± 2.2 months. Mean survival was 32.7 ± 2.4 months among patients with NYHA class II, 26.6 ± 3.4 months for NYHA class III, and 5.8 ± 1.1 months for NYHA class IV. The multivariate Cox proportional hazard regression model showed that NYHA class (HR = 3.42 , 95% CI: 1.36–8.65, P = 0.002), log-proBNP level (HR = 1.40 , 95% CI: 1.17–5.83, P = 0.03), and ENDO LSsys of the LV basal level (HR = 1.25 , 95% CI: 1.05–1.95, P = 0.004) were independent prognostic factors for CA. Conclusion. NYHA class, proBNP level, and ENDO LSsys of the LV basal level were independently associated with the survival of patients with CA. [ABSTRACT FROM AUTHOR]

Background. To investigate the value of SMO and GLI1 genes in the hedgehog pathway in malignant mesothelioma specimens. Further study on the expression and prognosis of SMO and GLI1 in malignant mesothelioma tissues and the relationship between the two and the molecular mechanisms of mesothelioma immunity and to further investigate the prognostic value of mesothelioma expression. Materials and Methods. Immunohistochemistry and RT-qPCR were applied to detect the expression of SMO and GLI1 proteins and mRNA in biopsy specimens and plasma cavity effusion specimens from malignant mesothelioma (n = 130) and benign mesothelial tissues (n = 50) and to analyze the clinicopathological significance and survival risk factors of SMO and GLI1 protein expression in mesothelioma. The mechanisms of mesothelioma cell expression and immune cell infiltration were investigated using bioinformatics methods. Results. SMO and GLI1 in mesothelioma tissues detected high concordance between the diagnostic results of mesothelioma biopsy specimens and plasma cavity effusion specimens. The expression levels of SMO and GLI1 protein and mRNA in mesothelioma tissues were higher than those in benign mesothelioma tissues. The expression levels of SMO and GLI1 protein were correlated with the age, site, and asbestos exposure history of patients with mesothelioma. The expression levels of SMO and GLI1 protein were correlated with the expressions of ki67 and p53 (P < 0.05). SMO and GLI1 gene expression levels were negatively correlated with good prognosis in mesothelioma patients (P < 0.05). Cox proportional risk model indicated that protein expressions of invasion, lymph node metastasis, distant metastasis, staging, and genes were independent prognostic factors of mesothelioma. The GEPIA database showed the overall survival rate and the disease-free survival rate of mesothelioma patients in the high SMO and GLI1 expression groups; the UALCAN database analysis showed lower SMO expression levels in mesothelioma patients with more pronounced TP53 mutations (P = 0.001); GLI1 gene expression levels were strongly correlated with lymph node metastasis in mesothelioma patients (P = 0.009). Timer database analysis showed that the mechanism of immune cell infiltration was closely related to SMO and GLI1 expression. The degree of immune cell infiltration was strongly correlated with the prognosis of mesothelioma patients (P < 0.05). Conclusion. The expression levels of both SMO and GLI1 proteins were higher than those of normal mesothelial tissues, and the mRNA expression levels also changed in the same direction. SMO and GLI1 gene expressions in mesothelioma were negatively correlated with age, site of occurrence, and history of asbestos exposure. Positive expression of SMO and GLI1 was negatively correlated with patient survival. The Cox proportional risk model showed that gender, history of asbestos exposure, site of occurrence, SMO, and GLI1 were independent prognostic factors for mesothelioma. The mechanism of immune cell infiltration in mesothelioma is closely related to the gene expression of both and the survival prognosis of mesothelioma patients. [ABSTRACT FROM AUTHOR]

Objectives. To analyze the effects of deep hyperthermia combined with intraperitoneal chemotherapy on liver-kidney function, immune function, and long-term survival in patients with abdominal metastases. Methods. A total of 88 patients with abdominal metastases confirmed in the hospital were enrolled as the research objects between August 2018 and August 2021. They were randomly divided into control group (n = 44) and observation group (n = 44). The control group was treated with intraperitoneal chemotherapy, while observation group was additionally treated with deep hyperthermia. The general clinical data of patients were recorded. The short-term and long-term curative effects were evaluated. The occurrence of side effects in both groups was recorded. Before and after treatment, levels of alanine transaminase (ALT) and aspartate transaminase (AST) were detected by full-automatic biochemical analyzer. The level of blood urea nitrogen (BUN) was detected by the urease electrode method. The level of serum creatinine (Scr) was detected by the picric acid method. The levels of CD3+, CD4+, CD8+, and NK cells were detected by BD FACSCalibur flow cytometer. Results. There was no significant difference in clinical data between the two groups (P > 0.05). In the observation group, ORR was significantly higher than that in the control group (54.55% vs 29.55%) (P < 0.05), OS was significantly longer than that in the control group (P < 0.05), and median survival time and mPFS were longer than those in the control group. After treatment, the levels of ALT, AST, BUN, and Scr were significantly increased in the control group (P < 0.05), but there was no significant difference in peripheral blood CD3+, CD4+, and CD4+/CD8+ ratio or count of NK cells before and after treatment (P > 0.05). Before and after treatment, there was no significant difference in the levels of ALT, AST, BUN, and Scr in the observation group (P > 0.05). After treatment, peripheral blood CD3+, CD4+, and CD4+/CD8+ ratio and count of NK cells were all increased in the observation group, significantly higher than those in the control group (P < 0.05). The incidence of chemotherapy side effects in the observation group was significantly lower than that in the control group (P < 0.05). Conclusion. The short-term and long-term curative effects of deep hyperthermia combined with intraperitoneal chemotherapy are good on patients with intraperitoneal metastases, with less damage to liver-kidney function. It is beneficial to enhance immune function of patients, with mild side effects. [ABSTRACT FROM AUTHOR]

EPAS1 plays an important role in the development and progression of multiple tumor types by interacting with a series of other molecules. However, the prognostic and diagnostic values of EPAS1 in acute myeloid leukemia (AML) remain unknown. Here, we systematically explored and clarified the potential functions of EPAS1 in AML using data from Xena Browser and TCGA database. The expression of EPAS1 was significantly lower in AML patients than that in healthy people. The GO, KEGG, GSEA, and GSVA were performed to explore the potential functions and signaling pathways. The survival analysis was conducted using Cox regression analysis and the Kaplan-Meier method. Immune cell infiltration was evaluated via single-sample GSEA (ssGSEA). The results of enrichment analyses suggested that low-EPAS1 expression was related to the initiation, development, and prognosis of AML. The immune microenvironment landscape in AML was described by ssGSEA. ROC analysis of EPAS1 showed high discrimination ability between AML patients and healthy people. Kaplan-Meier method indicated that low-EPAS1 expression correlated significantly with a poor overall survival. Multivariate Cox regression analysis revealed that both age and EPAS1 expression were independent prognostic factors in AML patients. Furthermore, the nomogram based on these two variables performed well in discrimination and calibration. In summary, our study may provide new insights into the molecular mechanisms underlying AML and demonstrate the diagnostic and prognostic value of EPAS1 in AML for the first time. [ABSTRACT FROM AUTHOR]

The prognosis of patients with colorectal cancer (CRC) is affected by invasion and metastasis. Leucyl-tRNA synthetase (LARS) was shown to be related to the growth and migration of lung cancer cells. Dickkopf 4 (DKK4) is known as a Wnt/β-catenin pathway inhibitor, and its upregulation was reported in several cancers. However, the clinical significance of LARS and DKK4 in human CRC has not been clearly defined. We investigated the expression of LARS and DKK4 by immunohistochemical staining in tissue microarrays from 642 primary CRC patients and analyzed the relationship between their expression and the clinicopathological characteristics of CRC patients. LARS and DKK4 expressions were not related to gender, age at surgery, histologic grade, size, tumor location, tumor invasion, or metastasis, but LARS expression was significantly correlated with TNM stage, N stage, and lymph node metastasis. DKK4 expression was inversely related to the TNM stage and N stage. Survival analysis demonstrated that the OS and DFS in the LARS high expression group were not different compared to the LARS low expression group. OS and DFS in the DKK4 high expression group were significantly higher than in the DKK4 low expression group. In addition, OS and DFS in the group with the combination of the LARS high/DKK4 low expression were significantly lower than in the LARS high/DKK4 high expression group. The low expression of DKK4 alone can be used as a predictor of relapse in CRC patients. In addition, DKK4 low expression in the case of LARS high expression can be used as a poor prognostic factor in CRC patients. Thus, our findings suggest that DKK4 alone or in combination with LARS at diagnosis may be a useful prognostic factor for CRC. [ABSTRACT FROM AUTHOR]

Objective. The purpose of this study was to evaluate the clinical efficacy of apatinib plus concurrent radiotherapy on carcinoma embryonic antigen (CEA) and vascular endothelial growth factor (VEGF) expression in patients with non-small-cell lung cancer (NSCLC) with oligometastases. Methods. This is a prospective randomized controlled trial. Sixty-four patients with oligometastatic NSCLC who were treated in the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2017 to January 2019 were randomly assigned into the control group and the study group, with 32 cases in each group. The control group was treated with stereotactic body radiotherapy (SBRT), and the study group was treated with apatinib. Results. The overall response rate (ORR) of the study group was significantly higher than that of the control group. The carcinoma embryonic antigen (CEA) and the vascular endothelial growth factor (VEGF) in the two groups were significantly decreased, with lower results in the study group compared to the control group. The 12-month and 24-month overall survival (OS) of the study group were significantly higher than those of the control group. There was no significant difference in progression-free survival (PFS) between the two groups. The median OS in the control group was 20.0 months, and the study group had not yet reached the median OS; the OS in the study group was significantly higher than that in the control group. There was no significant difference in adverse reactions between the two groups. Conclusion. For patients with oligometastatic lung cancer, apatinib combined with chemotherapy can significantly improve clinical efficacy, reduce tumor marker expression, and extend overall survival with good safety profiles. [ABSTRACT FROM AUTHOR]

Objectives. The most common subtype of renal cell carcinoma, clear cell renal cell carcinoma (ccRCC), has a high heterogeneity and aggressive nature. The basement membrane (BM) is known to play a vital role in tumor metastasis. BM-related genes remain untested in ccRCC, however, in terms of their prognostic significance. Methods. BM-related genes were gleaned from the most recent cutting-edge research. The RNA-seq and clinical data of the ccRCC were obtained from TCGA and GEO databases, respectively. The multigene signature was constructed using the univariate Cox regression and the LASSO regression algorithm. Then, clinical features and prognostic signatures were combined to form a nomogram to predict individual survival probabilities. Using functional enrichment analysis and immune-correlation analysis, we investigated potential enrichment pathways and immunological characteristics associated with BM-related-gene signature. Results. In this study, we built a model of 20 BM-related genes and classified them as high-risk or low-risk, with each having its anticipated risk profile. Patients in the high-risk group showed significantly reduced OS compared with patients in the low-risk group in the TCGA cohort, as was confirmed by the testing dataset. Functional analysis showed that the BM-based model was linked to cell-substrate adhesion and tumor-related signaling pathways. Comparative analysis of immune cell infiltration degrees and immune checkpoints reveals a central role for BM-related genes in controlling the interplay between the immune interaction and the tumor microenvironment of ccRCC. Conclusions. We combined clinical characteristics known to predict the prognosis of ccRCC patients to create a gene signature associated with BM. Our findings may also be useful for forecasting how well immunotherapies would work against ccRCC. Targeting BM may be a therapeutic alternative for ccRCC, but the underlying mechanism still needs further exploration. [ABSTRACT FROM AUTHOR]