Investigation of the Mechanism of and Its Associated Autophagy-Related Genes in Gastric Cancer.

PURPOSE

Semaphorin 5A () and autophagy-related genes (ARGs) are pivotal in the pathogenesis of gastric cancer (GC). However, the potential regulatory role of in autophagy its associated ARGs and the underlying molecular mechanisms remain unresolved.

PATIENTS AND METHODS

GC-related datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify differentially expressed genes (DEGs) between GC and control samples. The intersection of DEGs with ARGs produced candidate genes, which were further analyzed using Spearman correlation with to identify signature genes. Stratification of GC samples based on signature gene expression, followed by Kaplan-Meier survival analysis, identified key genes. Subsequent analyses, including gene set enrichment analysis (GSEA), immune infiltration, and immune checkpoint evaluation, were conducted on the key genes and . The mRNA expression level was quantified using real-time quantitative polymerase chain reaction (RT-qPCR).

RESULTS

Ninety candidate genes were identified for Spearman correlation with , revealing , and with correlation coefficients exceeding 0.3. Survival analysis underscored and as key genes due to significant prognostic differences. GSEA implicated , and in the ECM receptor interaction pathway. Immune infiltration analysis indicated a negative correlation of and with M1 macrophages, while exhibited the strongest association with the immune checkpoint (p < 0.05, cor = 0.43). The mRNA expression level of was significantly upregulated in AGS parental cells compared to GES-1 cells (p < 0.01), whereas and mRNA levels were markedly downregulated in AGS parental cells relative to GES-1 (p < 0.0001).

CONCLUSION

ARGs , associated with , were identified, and their prognostic significance in GC was demonstrated. Additionally, their regulatory mechanisms were further elucidated through immune infiltration analysis and molecular network construction, providing a theoretical foundation for future research on the molecular mechanisms in patients with GC.