Molecular subtype of gastric cancer based on apoptosis-related genes reveals differential immune microenvironment and intratumoral microorganisms distribution

作者：Xuan Yu, Yongfu Shao, Haotian Dong, Jianing Yan, Xinjun Zhang, Guoliang Ye · 发表于：BMC Cancer · 年份：2025 · DOI：10.1186/s12885-024-13411-2 · 被引用次数：6 · 研究领域：Ferroptosis and cancer prognosis、Cancer Mechanisms and Therapy、Cancer-related molecular mechanisms research

BACKGROUND: Gastric cancer (GC) is known for its high heterogeneity, presenting challenges in current clinical treatment strategies. Accurate subtyping and in-depth analysis of the molecular heterogeneity of GC at the molecular level are still not fully understood. METHODS: This study categorized GC into two subtypes based on apoptosis-related genes (ARGs) and investigated differences in tumor immune microenvironment, intratumoral microorganisms distribution, gene expression, and signaling pathways. Key prognostic genes related to apoptosis in GC were identified through random survival forest analysis, and their specific signaling mechanisms were explored. Expression levels of key genes were validated through PCR in paired GC tissues and cancer cell lines. Moreover, biological functions of these key genes were verified in vitro experiments. RESULTS: A consistent clustering of GC was conducted using 161 apoptosis-related genes (ARGs), resulting in the identification of two subtypes, C1 and C2. Subsequently, significant differences were found in the tumor immune microenvironment, intratumoral microorganisms, gene expression, signaling pathways, and protein interaction networks between the two subtypes. GPX3, PLAT, and CAV1 were identified as key prognostic genes related to apoptosis in GC, with a focus on their impact on disease progression-related pathways. Furthermore, PCR assays validated that these three key genes exhibited significantly low expression levels in both GC cel...