Key Genes and Signaling Pathways Associated with the Progression of Gastric Cancer

 Identification of Key Genes and Signaling Pathways Associated with the Progression of Gastric Cancer

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Abstract

Genomic features have been gradually regarded as part of the fundamentals to the clinical diagnosis and treatment for gastric cancer. However, the molecular alterations taking place during the progression of gastric cancer remain unclear. Therefore, identification of potential key genes and pathways in the gastric cancer progression is crucial to clinical practices. The gene expression profile, GSE103236, was retrieved for the identification of the differentially expressed genes (DEGs), followed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichments, gene set enrichment analysis (GSEA) and the protein-protein interaction (PPI) networks. Multiple bioinformatics platforms were employed for expression and prognostic analysis. Fresh frozen gastric cancer tissues were used for external validation. A total of 161 DEGs were identified from GSE103236. The PPI network-derived hub genes included collagen type I alpha 1 chain (COL1A1), tissue inhibitor of the metalloproteinases (TIMP1), Secreted Phosphoprotein 1 (SPP1), somatostatin (SST), neuropeptide Y (NPY), biglycan (BGN), matrix metallopeptidase 3 (MMP3), apolipoprotein E (APOE), ATPase H+/K+ transporting alpha subunit (ATP4A), lysyl oxidase (LOX). SPP1 (log rank p = 0.0048, HR = 1.39 [1.1–1.75]) and MMP3 (log rank p < 0.0001, HR = 1.77 [1.44–2.19]) were significantly associated with poor overall survival. Stage-specifically, both COL1A1 and BGN were correlated with significant in stage III and IV gastric cancer cases. LOX showed significant correlation with prognosis in stage I and stage II gastric cancer cases. Furthermore, cg00583003 of SPP1 and cg16466334 of MMP3 exhibited highly methylation level and significant prognostic values (SPP1: HR = 1.625, p = 0.013; MMP3: HR = 0.647, p = 0.011). Hub genes signature displayed a favorable prognostic value (p value = 5.227e-05). APOE demonstrated the highest correlation with CD8⁺ T cells, neutrophils, and dendritic cells whereas BGN had the highest correlation with macrophages. This study systematically explored the key genes and pathways involved in PGC and AGC, providing insights into therapeutic individualized management.