Construction of a Cuproptosis-Related Gene Signature for Predicting Prognosis in Gastric Cancer.

This study aimed to develop and validate a cuproptosis-related gene signature for the prognosis of gastric cancer. The data in TCGA GC TPM format from UCSC were extracted for analysis, and GC samples were randomly divided into training and validation groups. Pearson correlation analysis was used to obtain cuproptosis-related genes co-expressed with 19 Cuproptosis genes. Univariate Cox and Lasso regression analyses were used to obtain cuproptosis-related prognostic genes. Multivariate Cox regression analysis was used to construct the final prognostic risk model. The risk score curve, Kaplan-Meier survival curves, and ROC curve were used to evaluate the predictive ability of Cox risk model. Finally, the functional annotation of the risk model was obtained through enrichment analysis. Then, a six-gene signature was identified in the training cohort and verified among all cohorts using Cox regression analyses and Kaplan-Meier plots, demonstrating its independent prognostic significance for gastric cancer. In addition, ROC analysis confirmed the significant predictive potential of this signature for the prognosis of gastric cancer. Functional enrichment analysis was mainly related to cell-matrix function. Therefore, a new cuproptosis-related six-gene signature (ACLY, FGD6, SERPINE1, SPATA13, RANGAP1, and ADGRE5) was constructed for the prognosis of gastric cancer, allowing for tailored prediction of outcome and the formulation of novel therapeutics for gastric cancer patients.

Serum extracellular vesicle-derived miR-21-5p and miR-26a-5p as non-invasive diagnostic potential biomarkers for gastric cancer: A preliminary study.

PURPOSE: Gastric cancer is the most common malignancy worldwide and is the third leading cause of cancer-related deaths, urgently requiring an early and non-invasive diagnosis. Circulating extracellular vesicles may emerge as promising biomarkers for the rapid diagnosis in a non-invasive manner. METHODS: Using high-throughput small RNA sequencing, we profiled the small RNA population of serum-derived extracellular vesicles from healthy controls and gastric cancer patients. Differentially expressed microRNAs (miRNAs) were randomly selected and validated by reverse transcription-quantitative real-time polymerase chain reaction. Receiver operating characteristic curves were employed to assess the predictive value of miRNAs for gastric cancer. RESULTS: In this study, 193 differentially expressed miRNAs were identified, of which 152 were upregulated and 41 were significantly downregulated. Among the differently expressed miRNA, the expression levels of miR-21-5p, miR-26a-5p, and miR-27a-3p were significantly elevated in serum-derived extracellular vesicles of gastric cancer patients. The miR-21-5p and miR-27a-3p were closely correlated with the tumor size. Moreover, the expression levels of serum miR-21-5p and miR-26a-5p were significantly decreased in gastric cancer patients after surgery. CONCLUSIONS: The present study discovered the potential of serum miR-21-5p and miR-26a-5p as promising candidates for the diagnostic and prognostic markers of gastric cancer.

SQSTM1/p62 promotes the progression of gastric cancer through epithelial-mesenchymal transition.

Background: SQSTM1/p62 is an autophagy-related receptor protein that participates in regulating tumorigenesis and multiple signaling pathways. Gastric cancer (GC) is a common tumor in the digestive tract and continues to pose a significant threat to human health. Therefore, this study aims to investigate the impact of p62 on gastric cancer. Methods: Immunohistochemistry and Western blotting were employed to assess the expression level of the p62 protein in gastric cancer tissues and its correlation with prognosis. Subsequently, in vitro cell experiments were conducted to determine the role of p62 in gastric cancer cell proliferation, migration, and metastasis. Result: The expression of p62 in gastric cancer tissues was significantly higher than in normal tissues. The expression of p62 was positively correlated with poor prognosis in gastric cancer patients. In vitro cell experiments indicated that p62 promotes gastric cancer cell proliferation and migration. Mechanistically, elevated p62 expression induced epithelial-mesenchymal transition (EMT), leading to upregulation of E-cadherin and downregulation of N-cadherin and vimentin. Conclusion: This study provides novel and robust evidence for the mechanism by which elevated p62 expression promotes the progression of gastric cancer. It offers promising therapeutic targets for anti-tumor treatment strategies in gastric cancer patients.