Differential genetic mutations and immune cell infiltration in high‐ and low‐risk STAD: Implications for prognosis and immunotherapy efficacy

Abstract This study investigates genetic mutations and immune cell dynamics in stomach adenocarcinoma (STAD), focusing on identifying prognostic markers and therapeutic targets. Analysis of TCGA‐STAD samples revealed C > A as the most common single nucleotide variant (SNV) in both high and low‐risk groups. Key mutated driver genes included TTN, TP53 and MUC16, with frame‐shift mutations more prevalent in the low‐risk group and missense mutations in the high‐risk group. Interaction analysis of hub genes such as C1QA and CD68 showed significant correlations, impacting immune cell infiltration patterns. Using ssGSEA, we found higher immune cell infiltration (B cells, CD4 + T cells, CD8 + T cells, DC cells, NK cells) in the high‐risk group, correlated with increased risk scores. xCell algorithm results indicated distinct immune infiltration levels between the groups. The study's risk scoring model proved effective in prognosis prediction and immunotherapy efficacy assessment. Key molecules like CD28, CD27 and SLAMF7 correlated significantly with risk scores, suggesting potential targets for high‐risk STAD patients. Drug sensitivity analysis showed a negative correlation between risk scores and sensitivity to certain treatments, indicating potential therapeutic options for high‐risk STAD patients. We also validated the carcinogenic role of RPL14 in gastric cancer through phenotypic experiments, demonstrating its influence on cancer cell proliferation, invasion and migration. Overall, this research provides crucial insights into the genetic and immune aspects of STAD, highlighting the importance of a risk scoring model for personalized treatment strategies and clinical decision‐making in gastric cancer management.