Anti-PD-1/PD-L1 inhibitors provide a survival advantage over conventional therapies for treatment of advanced or metastatic cancer. However, the factors determining which patients benefit the most from anti-PD-1/PD-L1 inhibitors are unknown, making treatment-related decisions difficult. We performed a systematic review and meta-analysis of acquired data to assess the efficacy and toxicity of anti-PD-1/PD-L1 inhibitors in advanced and metastatic cancer. A thorough search strategy was applied to identify randomised controlled trials (RCTs) in Pubmed, Embase, Cochrane, and major conferences. Studies meeting predefined selection criteria were selected, and two independent investigators performed data extraction; overall survival (OS), progression-free survival (PFS), and overall response rate were compared between anti-PD-1/PD-L1 inhibitors and control therapies. We calculated the pooled response rate and 95% CIs of all-grade and high-grade (≥3) adverse effects and evaluated the within-study heterogeneity using subgroup, sensitivity, and meta-regression analyses. In final, we included eligible 35 RCTs (21047 patients). The main estimated hazard ratios (HRs) for OS and PFS were 0.76 (0.71–0.82) and 0.81 (0.73–0.89) in a random-effects model. The anti-PD-1/PD-L1 inhibitor group had a significantly high risk for all-grade immune-related adverse events. Anti-PD-1/PD-L1 inhibitors were identified as a preferable treatment option for advanced or metastatic cancer patients who are male, aged < 65 years, current or former smokers, had no CNS or liver metastasis, had not EGFR mutation, and had high PD-L1 expression.

Background: Colon cancer is one of the most common cancers in the world. Targeting biomarkers is helpful for the diagnosis and treatment of colon cancer. This study aimed to identify biomarkers in colon cancer, in addition to those that have already been reported, using microarray datasets and bioinformatics analysis. Methods: We downloaded two mRNA microarray datasets (GSE44076 and GSE47074) for colon cancer from the Gene Expression Omnibus (GEO) database and the most recent colon cancer data (COAD) from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) between colon cancer and adjacent normal tissues were determined based on these three datasets. Additionally, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and protein-protein interaction (PPI) network analysis. The hub genes in the PPI network were then selected and analysed. Results: We identified 150 DEGs and the GO enrichment analysis revealed that these DEGs were enriched in functions related to accelerating the cell cycle, promoting tumour cell accumulation, promoting cell division, positively regulating cell division, and negatively regulating apoptosis. The KEGG pathway analysis indicated that the DEGs were also involved in the cell cycle pathway. In the PPI network, 34 hub genes were found to be enriched in cell division. Prognostic analysis of the 34 hub genes revealed that eight genes (CCNB1, CHEK1, DEPDC1, ECT2, GINS2, HMMR, KIF14, and KIF18A) were associated with the prognosis of colon cancer. And our qRT-PCR results confirmed that DEPDC1, ECT2, GINS2, HMMR and KIF18A were highly expressed in colon cancer cells. Conclusions: The genes DEPDC1, ECT2, GINS2, HMMR, and KIF18A could serve as novel diagnostic biomarkers of colon cancer.

BACKGROUND:The protein 4.1 family is a family of cytoskeletal proteins that play an important role in maintaining normal cell morphology and cell adhesion, migration, division, and intercellular signaling. The main aim of this study was to explore th...

Objective: This study aims to comprehensively analyze the temporal trends and geographic disparities in the burden of seven digestive system neoplasms—esophageal cancer, stomach cancer, colon and rectum cancer, liver cancer, gallbladder and biliary tract cancer, pancreatic cancer, and benign and in situ intestinal neoplasms—among middle-aged and elderly populations from 1990 to 2021, and to project future trends through 2035. Methods: This study utilized data from the Global Burden of Disease (GBD) 2021 database to analyze the burden of seven digestive system neoplasms among middle-aged and elderly adults across 204 countries and territories from 1990 to 2021. Estimates of incidence, mortality, and disability-adjusted life years (DALYs) were extracted and stratified by year, sex, age group, region, and Socio-Demographic Index (SDI). Trends were evaluated using estimated annual percentage change (EAPC), and risk factors were analyzed using the GBD comparative risk assessment framework. Results: In 2021, colon and rectum cancer dominated the global burden of digestive system neoplasms. Trends from 1990 to 2021 revealed a clear split: the incidence of colon and rectum cancer (EAPC = 0.26, 95% CI 0.19 to 0.33), liver cancer (EAPC = 0.25, 95% CI 0.82 to 1.38), pancreatic cancer (EAPC = 0.55, 95% CI 0.53 to 0.57), and benign intestinal neoplasms (EAPC = 1.1, 95% CI 0.82 to 1.38) rose globally, while esophageal (EAPC = −0.92, 95% CI −1.06 to −0.79), stomach (EAPC = −1.63, 95% CI −1.71 to −1.55), and gallbladder/biliary tract cancers (EAPC = −0.28, 95% CI −0.31 to −0.25) declined. Regional hotspots for burden were East Asia and High-income Asia Pacific. Males generally faced higher burdens, except for gallbladder and biliary tract cancer. Key risk factors included smoking, alcohol consumption, dietary patterns, and metabolic factors such as high BMI and elevated fasting plasma glucose. Conclusions: The burden of digestive system neoplasms remains substantial in middle-aged and elderly adults, with significant regional differences. With the growing aging population, efforts should prioritize high-risk populations and invest in healthcare infrastructure in middle- and low-SDI regions to control established cancers. Additionally, implementing robust global prevention policies, such as expanding disease screening, raising public health awareness, and managing metabolic disorders, is essential to mitigate the rising tide of digestive system neoplasms.

Background Thymocyte selection-associated HMG-BOX (TOX) belongs to a family of transcription factors containing a highly conserved region of the high mobility group box (HMG-Box). A growing body of research has shown that TOX is involved in the occurrence and development of tumors and promotes T-cell exhaustion. We assessed the role of TOX with The Cancer Genome Atlas (TCGA) Pancancer Data. Methods TOX expression was examined with RNA-seq data from the TCGA and Genotype-Tissue Expression (GTEx) databases. The genetic alteration status and protein level of TOX were analyzed using databases, including the Human Protein Atlas (HPA), GeneCards, and STRING. The prognostic significance was estimated with survival data from the TCGA. Moreover, R software was used for enrichment analysis of TOX. The relationship between TOX and immune cell infiltration was assessed with the Tumor Immune Estimation Resource (TIMER) 2.0 database and the “CIBERSORT” method. The correlation between TOX and immune checkpoints was further explored. Immunohistochemical analysis was used to further verify the difference in TOX expression between cancerous and paracancerous tissues, and cell viability was evaluated using a CCK-8 assay. Results In most cancer types in the TCGA cohort, differential TOX expression was observed. The genetic alteration status and protein level of TOX were examined, and the prognosis of cancers was associated with TOX expression. Moreover, TOX levels were closely related to different immune-related pathways, immune cell infiltration and immune checkpoints. Additionally, significant differences in TOX expression between several cancerous and paracancerous tissues were validated. Furthermore, TOX clearly impacted the viability of cancer cells. Conclusions TOX, a potential biomarker for cancer, may be involved in the regulation of the immune microenvironment and can be used for new targeted drugs.