Decoding Gastric Cancer: An AI-Driven Transcriptomic Meta-Analysis

Gastric cancer (GC) remains a leading cause of global cancer mortality, necessitating deeper insights into its molecular mechanisms. This meta-analysis and systematic review integrated transcriptomic data from 28 studies (14 RNA-seq, 13 microarray) to identify critical genes and pathways driving GC progression. Leveraging AI-driven approaches for data harmonization and batch effect correction, we standardized raw datasets from public repositories (GEO, SRA, TCGA) and performed rigorous quality control. Differential expression analysis using edgeR and LIMMA identified 1,163 differentially expressed genes (DEGs), including CST1 (most up-regulated) and PGA3 (most down-regulated). Pathway enrichment revealed tumor proliferation (E2F targets, G2-M checkpoint), ECM remodeling (collagens, MMPs), immune evasion (CXCL chemokines), and metabolic reprogramming as key processes. Protein-protein interaction (PPI) network analysis highlighted hub genes such as AURKA, COL1A1, and IL6, while AI-enhanced clustering delineated functional modules linked to metastasis and prognosis. Survival and immune infiltration analyses underscored the clinical relevance of identified genes. Notably, ERBB4 down-regulation and collagen family up-regulation were mechanistically tied to apoptosis resistance and microenvironment stiffening. AI algorithms further aided in resolving dataset heterogeneity and prioritizing high-confidence biomarkers. This study provides a comprehensive transcriptomic landscape of GC, emphasizing the interplay between genetic drivers, tumor microenvironment, and immune evasion.