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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 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]

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]

Advanced gastric cancer is a highly aggressive malignancy. The available literature does not provide the prognostic value of ascites based on their degree, because most clinical trials exclude patients who present with massive ascites. Therefore, this study examined whether the presence or degree of ascites has a prognostic value in 124 patients with advanced gastric cancer. The degree of ascites was assessed using computed tomography and classified as none, small, moderate or massive. The overall survival (OS) was compared based on the presence or degree of ascites. Furthermore, a Cox proportional hazards analysis was performed to ascertain the predictors of OS. The cumulative 1-year and 2-year OS rates in patients without ascites were 43.5 and 20.2%, respectively, whereas those in patients with ascites were 29.1 and 13.6%, respectively (P=0.116). The cumulative 1-year and 2-year OS rates in patients without moderate or massive ascites were 39.5 and 20.9%, respectively; however, those in patients with moderate or massive ascites were 28.0 and 4.0%, respectively (P=0.027). Multivariate analysis showed that diffuse-type [hazard ratio (HR), 1.532; 95% confidence interval (CI), 1.002-2.343; P=0.049], moderate or massive ascites (HR, 2.153; 95% CI, 1.301-3.564; P=0.003) and chemotherapy (HR, 0.189; 95% CI, 0.101-0.352; P<0.001) were significant predictive factors of OS. In conclusion, the present study indicated that moderate or massive ascites may influence the OS of patients with advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Sarcopenia is a prognostic factor for patients with colorectal cancer and is commonly seen in elderly patients. The purpose of the present study was to demonstrate the impact of preoperative sarcopenia on the short- and long-term outcomes of curative surgery for treating colorectal cancer in elderly patients. Between 2016 and 2020, patients aged ≥80 years with colorectal cancer were investigated. The total muscle cross-sectional area was calculated using computed tomography imaging at the mid-3rd lumbar vertebra. Elder sarcopenia was identified using sex-specific cut-offs. Out of 106 elderly colorectal cancer patients, 27 patients were diagnosed with elder sarcopenia. Patients with elder sarcopenia had a reduced body mass index (19.7±2.5 vs. 22.5±2.9 kg/m2; P<0.01), an advanced pN stage (P<0.01) and an advanced stage (stage 3) (P=0.029). Elder sarcopenia had a negative impact on relapse-free survival (3-year, 78.4 vs. 91.1%; P=0.049) and overall survival (3-year, 73.0 vs. 93.9%; P=0.022). Propensity score-matched analysis was performed, matching 27 patients in each group to remove selection bias, which demonstrated elder sarcopenia had a negative impact on overall survival (3-year, 73.0 vs. 100%; P<0.01). Overall, elder sarcopenia was prevalent in 25% of elderly patients with colorectal cancer that received curative surgery, and it was a poor prognostic indicator in this patient population. [ABSTRACT FROM AUTHOR]

Rectal cancer is one of the most malignant tumors, and postoperative recurrence and metastasis are the main reasons for treatment failure. Lymph node metastasis is the main metastatic pathway of rectal cancer. The present study aimed to investigate the role of lateral lymph node dissection (LLND) in patients with rectal cancer using a meta-analysis. Articles in Chinese and English related to the application of LLND in patients with rectal cancer were retrieved and eligible studies were selected for data analysis. Evaluation indicators included the 5-year survival rate, recurrence rate, urinary system function and operation time. The random-effects model was utilized for the analysis. A total of 10 studies that met the eligibility criteria were selected, comprising 2,272 patients, including 1,101 cases in the LLND group and 1,171 cases in the non-LLND group. No significant difference was found between the two groups in terms of local recurrence rate, 5-year disease-free survival (DFS) rate, and DFS rate at the follow-up. It is noteworthy that cases in the LLND group had no significantly longer overall survival, but had a higher 5-year survival rate. However, cases in the LLND group had a longer operation time and worse urinary dysfunction. The results remained consistent throughout separate analyses for different research quality sources. The present meta-analysis showed that LLND provided a specific advantage in prolonging survival time. However, it was associated with prolonged operation time and an increased incidence of urinary dysfunction. [ABSTRACT FROM AUTHOR]

The aim of the present study was to assess the blood the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) as prognostic factors in breast cancer (BC) patients. A retrospective analysis of 436 BC patients who were treated at COI (Gliwice, Poland) between January 2005 and June 2018 was performed. The prognostic value [overall survival (OS)] of the pre-treatment PLR, NLR and MLR was assessed by univariate and multivariate analysis. The 5-year OS was lower in the NLR >2.65 compared with that in the NLR≤2.65 group (82.5 vs. 89.6%; P=0.053), and significantly lower in the subgroup of triple-negative breast cancer (TNBC; 70.3 vs. 89.3%; P=0.034) and in patients whose tumors had an estrogen receptor-negative [ER(−)] status (66.6 vs. 83.6%; P=0.018). The 5-year OS was lower in patients with PLR >190.9 compared with that in the PLR≤190.9 group (78.7 vs. 89.4%; P=0.020). A poor OS rate associated with an elevated PLR was also observed in the subgroups with TNBC (68.2 vs. 88.5%; P=0.032) and with ER(−) status tumors (57.7 vs. 83.6%, P=0.002). An elevated MLR (>0.28) was not associated with OS time (P=0.830). Multivariate analysis revealed that the NLR and PLR were insignificant negative prognostic factors, except for the subgroup of patients with ER(−) tumors, where an elevated NLR [hazard ratio (HR)=2.40; 95% confidence interval (CI): 1.20–4.80; P=0.013] and a higher PLR (HR=2.51; 95%CI: 1.23–5.14; P=0.012) were independent prognostic factors for poor OS together with lymph node metastasis ((HR=5.47; 95%CI: 2.46–12.15; P=0.0001 and HR=4.82; 95% CI: 2.15–10.78; P=0.0001), respectively. The present results revealed that an elevated NLR (>2.65) and PLR (>190.9) are associated with poor OS in BC patients. In the ER(−) subgroup of patients, an elevated NLR and PLR were significant independent prognostic factors. However, the MLR did not affect OS. [ABSTRACT FROM AUTHOR]

Currently, there are only a few risk assessment tools that provide predictions of survival duration for patients with gastric cancer (GC) receiving immunotherapy. The purpose of the present study was to develop and validate a nomogram that uses statistical data to predict survival and make risk assessments for patients with advanced staged GC. A total of 1,013 patients consisting of a development cohort (n=501) and validation cohort (n=512) collected during the time interval between January 2018 and June 2022 were included in the present study. The analysis consisted of the discrimination index, calibration plots and decision curve of the nomogram model. A total of 167 (33.33%) patients from the development cohort, and 158 (30.85%) from the validation cohort died during the observation period. The median overall survival (OS) of female patients was higher at 980 days (95% CI, 613-NA) compared with that of male patients, which was 748 days (95% CI, 597-NA; P=0.24). The median survival of patients with domestic immunotherapy was 789 (95% CI, 597-NA) days, which was lower compared with the imported immunotherapy group who had a median OS of 980 days (95% CI, 582-NA; P=0.22). A total of four independent predictors, age (HR=1.012; P=0.0245), histological grade (HR=1.395; P=0.016), immunotherapy cycles (HR=0.932; P=0.028) and line of first immunotherapy (HR=1.693; P=0.0003), were identified. The C-index was 0.64 and 0.67 for the development and validation cohorts, respectively. Patients who received more cycles of immunotherapy as the first-line treatment with highly differentiated tumor led to increase in the survival time of the patients. Thus, this nomogram could be used to determine the benefit of immunotherapies on patients at various stages of treatment of GC. [ABSTRACT FROM AUTHOR]

Network-based systems biology has become an important method for analysis of high-throughput gene expression data and gene function mining. The aim of the present study was to implement a weighted gene co-expression network analysis to screen genes that were significantly correlated with the clinical phenotype of endometrial cancer based on data from The Cancer Genome Atlas. By using the function 'pickSoftThreshold' in R software, the optimum soft thresholding power was determined to be 4. Subsequently, a total of 2,414 expressed genes were identified among 19,791 genes from 506 samples, which were divided into 24 modules according to the different expression patterns. After analyzing the correlation between the gene expression in these 24 modules and the clinical phenotype of endometrial cancer, the anoctamin 1 (ANO1) gene was selected for further analysis. The Chi-squared test indicated that ANO1 was significantly associated with age (P=0.047), histological type (P<0.001), clinical stage (P<0.001), pathological grade (P<0.001) and positive peritoneal washing (P=0.001) of endometrial carcinoma. Kaplan-Meier survival analysis revealed that a high level of ANO1 was significantly associated with a good prognosis for endometrial cancer patients. Univariate and multivariate Cox regression analysis indicated that ANO1 is an independent prognostic factor in endometrial cancer. Further characterization of the most relevant module containing ANO1 with the database for annotation, visualization and integrated discovery tool suggested that ANO1 is involved in various pathways, including metabolic pathways. The present study suggests that ANO1 may be a potential marker for good prognosis in endometrial cancer. [ABSTRACT FROM AUTHOR]

Cell division cycle 42 (CDC42) regulates immune escape, which predicts immune checkpoint inhibitor (ICI) treatment response in several types of cancer. The present study aimed to evaluate the potential of serum CDC42 in predicting the ICI treatment outcome in patients with advanced cervical cancer. A total of 46 patients with advanced cervical cancer who received ICI treatment with or without antiangiogenic agents were enrolled. Serum CDC42 was detected in all patients before treatment (baseline) and following two treatment cycles by enzyme-linked immunosorbent assay. CDC42 at baseline was elevated in patients with target lesion size ≥5 cm (P=0.020), pelvis metastasis (P=0.031) and lung metastasis (P=0.043). Following treatment, the objective response rate (ORR) and disease control rate (DCR) were 30.4 and 78.3%, respectively. Meanwhile, the median progression-free survival (PFS) and overall survival (OS) were 5.8 and 13.1 months. CDC42 at baseline was decreased in patients achieving ORR (P=0.042) but not DCR (P=0.055). PFS (P=0.006) and OS (P=0.019) were decreased in patients with baseline CDC42 ≥600 pg/ml. After two treatment cycles, CDC42 was generally reduced (P<0.001). CDC42 following two treatment cycles was more significantly decreased in patients with ORR (P=0.032) and DCR (P=0.019). Multivariate Cox's regression analysis showed that CDC42 ≥600 pg/ml following two treatment cycles was associated with the shorter PFS (P=0.022, hazard ratio=2.469) and OS (P=0.013, hazard ratio=4.166). Serum CDC42 was reduced after treatment; high expression following treatment reflected a lower possibility of achieving treatment response and poorer survival in patients with advanced cervical cancer. [ABSTRACT FROM AUTHOR]

At present, it is well known that natriuretic peptides may be produced by cancer cells. Stimulation of N-terminal pro B-type natriuretic peptide (NT-proBNP) synthesis may be a reaction to activity of several proinflammatory cytokines. NT-proBNP is also a marker of myocardial damage during cardiotoxic chemotherapy by anthracyclines. The present study aimed to analyze the association between NT-proBNP and patient/disease characteristics in patients without cardiac symptoms. The present clinical study included 112 patients with cancer who were undergoing anticancer therapy between December 2017 and December 2021. From each patient, peripheral blood was obtained for detection of NT-proBNP before any therapy, after therapy and 1 year after the first sample. NT-proBNP was examined using an immunochemical method. The mean ± SEM value of NT-pro-BNP in the first, second and third sample was 561.0±75.1, 1,565.4±461.1 and 1,940.7±581.1 ng/l. A total of 15 (13.4%), 27 (24.1%) and 25 (30.1%) patients had elevated levels of NT-pro-BNP in the first, second and third sample above the normal value adjusted to age. It was observed that NT-proBNP was increased in older patients and in patients with progressive metastatic disease with poor prognosis. Patients with non-elevated NT-proBNP in the second and third sample had significantly improved OS compared with patients with elevated NT-proBNP [hazard ratio (HR), 0.47; 95% CI, 0.26-0.85; P=0.002 for the second sample; and HR, 0.29; 95% CI, 0.14-0.60; P=0.0000007, for the third sample]. The baseline NT-proBNP value was not prognostic for OS (HR, 0.98; 95% CI, 0.50-1.92; P=0.96). The present results suggest that the level of NT-proBNP was associated with the extent of oncologic disease. Higher levels were associated with progression of metastatic disease and shorter overall survival. [ABSTRACT FROM AUTHOR]

Little progress has been made in the treatment of advanced cancer. Dendritic cells (DCs) plus cytokine-induced killer (CIK) cells have exhibited antitumor effects. Thus, the aim of the present study was to evaluate the clinical efficacy of DC-CIK cell treatment in patients with advanced cancer. A paired study including 57 patients treated with DC-CIK cells (DC-CIK group) and 33 patients treated with best supportive care alone (BSC group) was performed. The patients in the DC-CIK group were matched to those in the control group in terms of sex, age, tumor type and clinical stage. T-cell subsets were detected and overall survival (OS) was compared between the two groups. The results demonstrated that CD4+/CD25+ and CD8+/CD28- subsets significantly decreased following DC-CIK immunotherapy (P<0.05). The CD3+, CD3+/CD8+, CD8+/CD28+ and CD3+/CD56+ T-cell subsets were significantly increased in the DC-CIK group compared with the BSC group, while the CD8+/CD28- subset was significantly decreased. Univariate analysis demonstrated that a lower CD8+/CD28- and a higher CD8+/CD28+ ratio were associated with prolonged OS in advanced cancer patients. In addition, DC-CIK treatment administration, age (>60 vs. <60 years), clinical stage and the frequency of CIK treatment significantly affected the OS of patients in the DC-CIK group. A CD8+/CD28- ratio of <21.12 was found to decrease the hazard ratio (HR) of OS to 0.50 [95% confidence interval (CI): 0.29-0.87] and a CD8+/CD28+ ratio >9.04 was found to decrease the HR of OS to 0.45 (95% CI: 0.21-0.98). No serious side effects were observed in the DC-CIK group. Taken together, these data indicate that DC-CIK infusions were able to change the ratios of the T-cell subsets, which increased the T helper cell and cytotoxic T lymphocyte subsets, while it decreased regulatory T lymphocyte subsets. Thus, this method of immunotherapy was found to improve the imbalance in the immune system and prolong the OS in patients with advanced cancer. [ABSTRACT FROM AUTHOR]

Pembrolizumab has been widely used to treat advanced urothelial carcinoma that has progressed after first-line platinum-based chemotherapy. Because its clinical benefits are limited, biomarkers that can predict a good response to pembrolizumab are required. The prognostic nutritional index (PNI), calculated using the serum albumin level and peripheral lymphocyte count, has been evaluated as a predictive biomarker in cancer immunotherapy. The present study investigated the application of PNI as a predictive biomarker for pembrolizumab response in patients with advanced urothelial cancer. A retrospective study was conducted on 34 patients treated with pembrolizumab at Shiga University of Medical Science Hospital between January 2018 and July 2022. The posttreatment PNI (post-PNI) was calculated within 2 months of starting pembrolizumab. The present study investigated the association between post-PNI and objective response, overall survival (OS) and progression-free survival (PFS). The patient cohort was stratified into two categories, high and low post-PNI groups, with a cutoff value of post-PNI at 40. The higher post-PNI group demonstrated a better disease control rate than the lower post-PNI group (complete response + partial response + stable disease, 75 vs. 21%, P=0.004). Regarding median OS, the higher post-PNI group exhibited a significantly longer survival time than the lower post-PNI group (23.1 vs. 2.9 months, P<0.001). Similarly, the higher post-PNI group exhibited a significantly longer PFS than the lower post-PNI group (10.2 vs.1.9 months, P<0.001). Multivariate analysis showed that a higher post-PNI value was an independent predictor for OS (hazard ratio, 0.04; 95% confidence interval, 0.01–0.14; P<0.001) and PFS (hazard ratio, 0.12; 95% confidence interval, 0.04–0.35; P<0.001). The present study indicated that the post-PNI was a predictor of favorable clinical outcomes in patients treated with pembrolizumab for advanced urothelial carcinoma. [ABSTRACT FROM AUTHOR]

CD8+ tumor-infiltrating lymphocytes have been regarded as potential biomarkers for cancer prognosis, while the prognostic effect of CD8+ tumor-infiltrating T cells remains controversial in breast cancer. In the present study, a meta-analysis was performed to evaluate the prognostic value of CD8+ T cells in breast cancer and the associations between CD8+ T cells and the pathological characteristics. The PubMed, Embase and the Cochrane Library were systematically searched entries added from the establishment of the database to November 2021 and prospective or retrospective studies of patients with breast cancer were included. The Newcastle-Ottawa Scale was used to assess the quality of evidence for each study. STATA 15.1 was used for the data analysis. A total of 14 studies comprising 22,222 patients were included in the final analysis and the pooled results suggested that a high CD8+ T-cell infiltration level was significantly related to better overall survival [hazard ratio (HR)=0.70, 95% confidence interval (CI): 0.60-0.82, P<0.001] and disease-free survival (HR=0.63, 95% CI: 0.49-0.81, P<0.001) for patients with breast cancer. In addition, a high CD8+ T-cell infiltration level was significantly associated with decreased expression of estrogen receptor [odds ratio (OR)=1.92, 95% CI: 1.30-2.85, P=0.001] and progesterone receptor (OR=1.66, 95% CI: 1.14-2.42, P=0.008), and increased human epidermal growth factor receptor 2 expression (OR=0.79, 95% CI: 0.66-0.94, P=0.010) in patients with breast cancer, while there was no significant association between CD8+ T-cell infiltration and age, tumor size or lymph node status of patients with breast cancer (P>0.05). In conclusion, CD8+ T-cell infiltration is of prognostic value in patients with breast cancer. High levels of CD8+ T-cell infiltration were related to improved prognosis, including OS and DFS, in patients with breast cancer. [ABSTRACT FROM AUTHOR]

C-X-C motif chemokine ligand 12 (CXCL12) has been suggested as a possible biomarker of poor prognosis in patients with various malignancies. However, the association between tumor expression of CXCL12 and survival of patients with colorectal cancer (CRC) remains to be comprehensively analyzed. A meta-analysis to systematically evaluate this association was performed in the present study. Relevant cohort studies were retrieved by searching the PubMed, Embase and Web of Science databases from inception to March 22, 2022. A conservative random-effect model incorporating the possible influence of between-study heterogeneity was used to pool the results. A total of 14 cohort studies that included 2,060 patients with CRC contributed to the meta-analysis, and 1,055 (51.2%) of them had higher tumor expression levels of CXCL12. Pooled results showed that a higher tumor expression level of CXCL12 was associated with poor overall survival [hazard ratio (HR), 1.74; 95% confidence interval (CI), 1.29-2.34; P<0.001; I2, 33%] and progression-free survival (HR, 2.00; 95% CI, 1.47-2.73; P<0.001; I2, 33%). Subgroup analyses showed that the association between higher cancer expression levels of CXCL12 and poor survival in patients with CRC was not significantly affected by the country of the study, the location of the tumor, the cancer stage or the methods used for measuring tumor CXCL12 levels (all P>0.05). In conclusion, the study found that a higher tumor expression level of CXCL12 was associated with the poor survival of patients with CRC. Studies are warranted to determine if CXCL12-targeted intervention could improve the prognosis of patients with CRC. [ABSTRACT FROM AUTHOR]

The present study aimed to assess the correlation of C-X-C motif chemokine ligand (CXCL)1, CXCL2, CXCL8, CXCL13 and CXCL14 with clinicopathological features and survival profile in patients with colorectal cancer (CRC). Patients with primary CRC (n=232) were retrospectively reviewed, with their tumor tissue specimens acquired from the Department of Pathology (The First Hospital of Jilin University, Changchun, China), their demographic data and preoperative tumor features collected from the hospital database, and their survival data obtained from the follow-up documents. Tumor CXCL expression was detected by immunohistochemistry (IHC). Based on the total IHC score, the expression of CXCL1, CXCL2, CXCL8, CXCL13 and CXCL14 was categorized as low expression (IHC score ≤3) and high expression (IHC score >3). CXCL1 (51.3% high and 48.7% low), CXCL2 (59.9% high and 40.1% low), CXCL8 (44.4% high and 55.6% low), CXCL13 (40.9% high and 59.1% low) and CXCL14 (31.0% high and 69.0% low) were expressed in CRC tumor tissues, and their expression levels were correlated with each other, except between CXCL8 and CXCL14, and between CXCL13 and CXCL14. CXCL1 was associated with a larger tumor size, and an advanced T stage, N stage and Tumor-Node-Metastasis (TNM) stage. CXCL2 was associated with an advanced N stage and TNM stage, and CXCL8 was associated with a greater T stage and TNM stage. CXCL13 was associated with a greater T stage, N stage and TNM stage, while CXCL14 was not associated with any clinical characteristics. As for survival, CXCL1, CXCL2, CXCL8 and CXCL13, but not CXCL14, were associated with poor overall survival (OS) rate, and further multivariate Cox's regression model analysis revealed that CXCL1 independently predicted unfavorable OS in patients with CRC. Overall, CXCL1, CXCL2, CXCL8 and CXCL13 have good potential as an indicator for tumor features and survival in patients with CRC. [ABSTRACT FROM AUTHOR]

An increased mean platelet volume (MPV) is an early marker of platelet activation. MPV was also shown to be associated with the pathophysiological characteristics of various types of cancer. A previous study demonstrated that MPV was significantly associated with the overall survival (OS) of patients with advanced non-small-cell lung cancer (NSCLC). However, there has been no analysis of the prognostic effect of MPV on patients with resected NSCLC. The aim of this study was to evaluate the contribution of MPV to the survival of patients with completely resected NSCLC. We retrospectively analyzed 308 consecutive patients with NSCLC who underwent curative resection at Kitano Hospital. The associations between MPV and clinicopathological factors were assessed. We also evaluated the effect of MPV on survival, using the two-tailed log-rank test and the Cox proportional hazards model. A MPV value of 8.50 fl was considered to be the optimal cut-off value for prognosis. A low MPV was not associated with any other clinicopathological factors. The two-tailed log-rank test demonstrated that patients with a low MPV experienced a shorter disease-free survival (DFS) and overall survival (OS) (P=0.011 and 0.001, respectively), compared to those with a high MPV. The multivariate analysis demonstrated that a low MPV was an independent unfavorable prognostic factor for DFS and OS [hazard ratio (HR)=1.713; 95% confidence interval (CI): 1.070-2.742, P=0.025; and HR=2.835; 95% CI: 1.304-6.163, P=0.009, respectively)]. Therefore, we demonstrated that a low MPV predicted an unfavorable prognosis in patients with NSCLC following curative resection. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to investigate alternative endpoints to the 5-year overall survival (OS) and locoregional control (LRC) for nasopharyngeal carcinoma (NPC). A total of 2,450 NPC patients were enrolled in this study, including 1,842 patients treated with two-dimensional (2D) radiotherapy (RT), 451 treated with 3D conformal RT (CRT) and 157 treated with intensity-modulated RT (IMRT). We sequentially calculated the 1-, 2-, 3- and 4-year survival rates using a life table and compared these with the 5-year survival rate using the McNemar method, with the survival rate of the last indifferent comparison being considered as the alternative endpoint. For 2D RT, stage I patients exhibited similar survival rates at 1 and 5 years (98.9 vs. 94.4%, respectively; P=0.125 for both OS and LRC); stage N3 patients exhibited similar 4-year OS (55.2 vs. 53.5%; P=1.000) and 2-year LRC (78.3 vs. 71.2%; P=0.125) to the 5-year OS and LRC. For IMRT, the 1-, 2-, 3-, 4- and 5-year OS and LRC rates in stage I/II NPC patients were 100, 98, 96, 94 and 94% for OS and 100, 98, 96, 96 and 96% for LRC, respectively. No significant differences were observed for all the comparisons. For stage III/IV NPC patients treated with IMRT, the 1-, 2-, 3-, 4- and 5-year rates were 99.1, 96.3, 92.5, 88.8 and 85.0% for OS and 98.1, 97.2, 95.3, 90.7 and 89.7% for LRC, respectively. Only the 4-year OS and LRC rates were indifferent from those at 5 years (P=0.125 for OS and P=1.00 for LRC). In conclusion, the 1-year OS and LRC for stage I NPC patients treated with 2D RT or stage I/II NPC patients treated with IMRT, the 4-year OS and 2-year LRC for stage N3 NPC patients treated with 2D RT and the 4-year OS and LRC for stage III/IV NPC patients treated with IMRT were determined as the alternative endpoints to the 5-year OS and LRC for NPC patients. [ABSTRACT FROM AUTHOR]

Long non-coding (lnc)RNAs have been recognized as important regulators in gastric cancer. lncRNA GAS8-AS1 is considered a tumor suppressor in multiple types of cancer, such as papillary thyroid carcinoma, ovarian cancer and colorectal cancer. However, the specific role of GAS8-AS1 in gastric cancer remains to be fully elucidated. The aim of the present study was to investigate the role of GAS8-AS1 in gastric cancer and its potential underlying mechanisms of action. The expression levels of GAS8-AS1, microRNA (miR)-21-3p, PTEN and pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) in gastric cancer and non-cancerous tissues, as well as in gastric cancer cell lines, were detected using reverse transcription-quantitative PCR. Cell proliferation was detected by using a Cell Counting Kit-8 assay. Cell migration and invasion were detected using a Transwell assay. Results of the present study demonstrated that the expression levels of GAS8-AS1 in gastric cancer tissues were significantly decreased, whereas its expression did not differ among cancer tissues at different clinical stages. Low expression levels of GAS8-AS1 predicted poor 5-year survival rates for 70 patients with gastric adenocarcinoma from the Affiliated Hospital of Xuzhou Medical University (Xuzhou, China) during patient follow-up. In addition, the expression levels of miR-21-3p were markedly increased in cancer tissues, and miR-21-3p expression was negatively associated with the expression of GAS8-AS1. The direct interaction between GAS8-AS1 and miR-21-3p was predicted using the starBase database and was confirmed by using an RNA pull-down assay. In gastric cell lines, the overexpression of GAS8-AS1 reduced the expression levels of mature miR-21-3p but did not affect the expression of miR-21-3p precursor, while the overexpression of miR-21-3p did not, in turn, affect the expression of GAS8-AS1. In addition, the overexpression of GAS8-AS1 inhibited cancer cell proliferation, while the overexpression of miR-21-3p promoted cancer cell proliferation and attenuated the effects of GAS8-AS1. Overexpression of miR-21-3p promoted cancer cell migration and invasion, whereas overexpression of GAS8-AS1 did not affect cell migration or invasion. In summary, results of the present study have demonstrated that GAS8-AS1 acts as a tumor suppressor in gastric cancer, and it may inhibit cancer cell proliferation by downregulating miR-21-3p. [ABSTRACT FROM AUTHOR]

Small heterodimer partner (SHP) plays an essential role in the regulation of innate immune and inflammatory responses. The aim of the present study was to identify whether SHP levels are associated with cancer immunology and treatment outcomes in rectal cancer. SHP expression was analyzed via gene set enrichment analysis and the OncoLnc database. In addition, immunohistochemistry and reverse transcription-quantitative PCR analyses were performed on the tissues of patients with locally advanced rectal cancer, and the associations of SHP expression with the clinicopathological and hematological features or treatment response to preoperative radiochemotherapy (pRCT) were analyzed retrospectively. Furthermore, the present study investigated whether SHP expression correlated with immune infiltration levels and immune checkpoint molecules in rectal cancer. The results revealed that low SHP mRNA expression was significantly associated with an inflammatory response and poor prognosis. The nuclear expression of SHP was associated with clinical N stage, neutrophil count, lymphocyte count, neutrophil-lymphocyte ratio and complete pathologic response following pRCT. The low nuclear expression of SHP was associated with poor overall and distant metastasis-free survival (DMFS). In multivariate analysis, the low nuclear expression of SHP was identified as a significant independent prognostic factor for DMFS and a marginally significant prognostic factor for overall survival in rectal cancer. Furthermore, patients with low SHP expression exhibited higher neutrophil and CD8+ T cell infiltration levels and higher PD-L1 expression in rectal adenocarcinoma. These results indicate that SHP may act as an anti-inflammatory mediator via the regulation of systemic and local immune responses in rectal cancer. Moreover, SHP might be useful a potential marker or therapeutic target in rectal cancer. [ABSTRACT FROM AUTHOR]

The present study assessed plasma IgG in patients with metastatic recurrent breast cancer (mrBC) that is reactive to various T-cell epitope peptides of prostate-related antigens (PRAs), such as prostate-specific antigen, prostate-specific membrane antigen and prostate acid phosphatase. Patients were treated with personalized peptide vaccines (PPVs) which were selected and administered from a panel of candidate peptides based on human leukocyte antigen-types and prevaccination IgG levels to each peptide. The peptide panel consisted of 27 cytotoxic T-lymphocyte-epitope peptides derived from tumor-associated antigens, not including PRA. PRA peptides and peptide panels were retrospectively analyzed in 77 PPV-treated patients. The results revealed that PRA reactive IgG levels were increased after vaccination in 31 of the 97 patients included in the present study. Although there was no significant association between anti-PRA peptide levels and progression-free survival (PFS) or overall survival, anti-PRA peptide levels were significantly associated with PFS (P=0.009) in estrogen-receptor positive (ER+) patients with cancer. The results suggested that plasma anti-PRA IgG levels may be a useful prognostic marker for monitoring PPVs, particularly for ER+ patients with mrBC (trial registration no. from the UMIN Clinical Trials Registry, UMIN000001844). [ABSTRACT FROM AUTHOR]

Several studies have investigated the prognostic significance of programmed cell death ligand 1 (PD-L1)-positive expression in the tumor cells (TC) of patients with lung cancer. However, tumor-infiltrating immune cell (TIIC)-based PD-L1 expression and its prognostic value remain controversial. The present meta-analysis was performed on 11 studies comprising 2,685 patients, which were identified by a systematic search on the PubMed, PMC, Web of Science and Embase databases. The databases were searched for published articles up to October 30, 2020. The studies that evaluated overall survival (OS) or disease-free survival (DFS) expressed as hazard ratios (HRs) in the PD-L1 TIIC of patients with lung cancer were analyzed. All statistical analyses were conducted using Stata software, version 16.0. The results demonstrated that PD-L1 expression in TIICs was not associated with OS [HR=0.98; confidence interval (CI)=0.73-1.33; P=0.53] and DFS (HR=1.05; CI=0.63-1.77; P=0.42) for all the cohort included in the study. However, subgroup analysis revealed that PD-L1 TIICs were associated with improved OS in lung squamous cell carcinoma (HR=0.76; CI=0.58-0.99; P=0.04), while poorer DFS was observed in lung adenocarcinoma (HR=1.30; CI=1.19-1.43; P=0.008) and at the >1% staining cutoff value (HR=1.56; CI=1.12-2.16; P=0.03). However, poor OS (P=0.21) and DFS (P=0.14) were observed in Asian populations, while DFS (P=0.07) for only-membrane staining was not statistically significant. The results of the present study suggested that adding PD-L1 TIICs to the existing diagnostic algorithm may help to guide patient selection for anti-PD-1/PD-L1 therapy. Future large-scale studies are warranted for confirmation of the present findings. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) have been indicated to have important roles in the development of malignant tumors. In the present study, the expression of HIT000218960 in gastric cancer (GC) tissues was assessed and its clinical significance was analyzed. It was revealed that HIT000218960 was highly expressed in GC tissues and HIT000218960 levels in GC tissues from 103 cases were positively correlated with high mobility group AT-hook 2 (HMGA2) mRNA expression. Furthermore, HIT000218960 was significantly associated with tumor diameter, TNM stage, histological grade, the number of lymph nodes with metastasis and HMGA2 expression in tumor tissues of patients with GC. The results of the univariate and multivariate Cox regression analysis indicated that HIT000218960 expression was a factor affecting the prognosis of patients with GC. In addition, patients with GC with lower HIT000218960 or HMGA2 expression had more favorable 3-year survival, while HIT000218960 expression did not affect the 3-year overall survival of patients with GC with different levels of HMGA2 expression. In conclusion, HIT000218960 was highly expressed in patients with GC and was related to poor prognosis. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to analyze the feasibility and safety of radiosensitization using hydrogen peroxide for cervical cancer. In superficial tumors, breast cancer and hepatocellular carcinoma, the safety and effectiveness of radiosensitization has been reported; to the best of our knowledge, however, there are no reports on cervical cancer. A total of 20 patients with cervical cancer were recruited. Inclusion criteria were as follows: Patients who required radical external beam radiotherapy (RT); ineligible for or refused brachytherapy; age, ≥20 years; no hematogenous metastasis; Eastern Cooperative Oncology Group Performance Status up to 2; and had not undergone prior treatment. Hydrogen peroxide was used twice a week in combination with RT. A 3% hydrogen peroxide solution-soaked gauze was inserted into the vagina during RT. A total of 45 Gy was delivered in 25 fractions to the whole pelvis with a boost of 10 Gy in 5 fractions if pelvic or para-aortic metastatic lymph nodes were observed. Ultimately, 18 patients were evaluated. Among the 17 patients (excluding one patient with tumor in situ), the one- and two-year overall survival rates were both 90% in patients with stage I/II and 86% in stage III/IV cervical cancer. The adverse events were well tolerated with no severe acute or late adverse events. Although limited by small sample size, short observation time and low radiation dose, the present study demonstrated that radiosensitization treatment may be an option for patients who cannot undergo brachytherapy. The study was retrospectively registered at the university hospital medical information network center (no. UMIN000039045) on January 6, 2020. [ABSTRACT FROM AUTHOR]

The fibrinogen-to-albumin ratio (FAR), reflecting the systemic coagulation, nutritional and inflammation status of patients, has matured into a prognostic marker for several tumor types. However, only a few studies have assessed the utility of the FAR as a prognostic indicator in patients with advanced gastric cancer (GC) receiving first-line chemotherapy. In the present study, 273 patients with advanced GC who received first-line chemotherapy between January 2014 and January 2019 at the Cancer Hospital of China Medical University (Shenyang, China) were retrospectively analyzed. Using the cut-off values determined by receiver operating characteristic (ROC) analysis, the patients were divided into low-FAR (≤10.03) and high-FAR (>10.03), low-fibrinogen (<3.8 g/l) and high-fibrinogen (≥3.8 g/l), and low-albumin (<40.55 g/l) and high-albumin (≥40.55 g/l) groups. The associations of the pretreatment FAR and clinicopathological characteristics with progression-free survival (PFS) and overall survival (OS) were evaluated. In order to estimate the prognostic value of the FAR for patients with poor prognosis or normal fibrinogen and albumin levels, subgroup analyses were performed. The FAR had a higher area under the ROC curve (0.690; 95% CI: 0.628–0.752; P<0.001) compared with either fibrinogen or albumin alone, which are common indicators of coagulation, nutritional and inflammatory indices. A high FAR was significantly associated with a more advanced stage, peritoneal metastasis, increased CA72-4 levels and anemia (all P<0.05). On survival analysis, a low FAR was associated with a longer PFS and OS compared with a high FAR (202 vs. 130 days and 376 vs. 270 days, respectively; both P<0.001), while the hazard ratio (HR) and P-values of the FAR were lower compared with those of fibrinogen and albumin alone on multivariate analysis (PFS: HR=0.638, 95% CI: 0.436–0.932, P=0.020; OS: HR=0.568, 95% CI: 0.394–0.819, P=0.002). Subgroup analysis indicated that among patients with poor prognosis, including multiple metastases, TNM stage IV and abnormal CA72-4 levels, the FAR may be used as an accurate prognostic marker (all P<0.05), and may also reliably identify patients with poor prognosis among those with normal fibrinogen and albumin levels (all P<0.001). The FAR was indicated to be a valuable marker for predicting PFS and OS in patients with advanced GC receiving first-line chemotherapy and is superior to either fibrinogen or albumin alone. [ABSTRACT FROM AUTHOR]