Clinicopathological significance of histological diversity in gastric adenocarcinoma with primitive enterocyte phenotype: A methylation-driven aggressive entity

Figure 5 Multi-omics profiling reveals methylation-driven molecular features of gastric adenocarcinoma with primitive enterocyte phenotype. A: Heatmap illustrating the top 50 differentially expressed genes across gastric adenocarcinoma with primitive enterocyte phenotype (GAPEP) (blue), conventional gastric cancer (CGC) (orange), and CGC expressing primitive phenotypic markers (purple) highlights distinct gene expression patterns, with GAPEP forming a separate cluster; B: Box plots confirm significant upregulation of methylation regulators (TET, DNMT3, and EZH2) in GAPEP compared to CGC expressing primitive phenotypic markers and CGC; C: Gene Ontology analysis detailing the biological processes, cellular components, and molecular functions, with results underscoring the critical role of “methyl-CpG binding” in GAPEP development (left). Additionally, Kyoto Encyclopedia of Genes and Genomes pathway analysis identified key signaling pathways associated with GAPEP (right); D: Comparative analysis showing LGLS2 and SFTA2 as the only two genes with statistically significant differential expression between hepatoid adenocarcinoma and gastric adenocarcinoma with enteroblastic differentiation. GAPEP: Gastric adenocarcinoma with primitive enterocyte phenotype; CGC: Conventional gastric cancer; CGC-P: CGC expressing primitive phenotypic markers; HAC: Hepatoid adenocarcinoma; GAED: Gastric adenocarcinoma with enteroblastic differentiation.