Identification and validation of key genes associated with pathogenesis and prognosis of gastric cancer

Abstract

Background Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide. However, the precise mechanisms and specific biomarkers of GC have not been fully elucidated. We therefore sought to identify and validate the genes associated with GC. Methods RNA sequencing was performed on gastric tissue specimens from 10 cases each of non-atrophic gastritis (NAG), intestinal metaplasia (IM), and GC. Validation of gene expression was conducted through immunohistochemistry (IHC) staining. The Kaplan–Meier Plotter database was utilized to screen genes associated with prognosis, while protein–protein interaction analysis was conducted to identify hub genes. Results In GC-IM, the differentially expressed genes (DEGs) were predominantly enriched in pathways related to ECM-receptor interaction, focal adhesion, PI3K-Akt pathway, and pathways in cancer. Conversely, in IM-NAG, the DEGs were primarily enriched in pathways associated with fat digestion and absorption, pancreatic secretion, and retinol metabolism. IHC staining revealed elevated expression levels of KLK7 and KLK10 in GC. Specifically, KLK7 expression was found to be correlated with differentiation (P = 0.025) and depth of invasion (P = 0.007) in GC, while both KLK7 and KLK10 were associated with the overall survival (P < 0.05). Furthermore, a total of ten hub genes from DEGs in GC-NAG (COL6A2, COL1A1, COL4A1, COL1A2, SPARC, COL4A2, FN1, PCOLCE, SERPINH1, LAMB1) and five hub genes in IM-NAG (SI, DPP4, CLCA1, MEP1A, OLFM4) were demonstrated to have a significant correlation with the prognosis of GC. Conclusions The present study successfully identified and validated crucial genes associated with GC, providing valuable insights into the underlying mechanisms of this disease. The findings of this study have the potential to inform clinical practice.

Keywords

• Gastric cancer
• Pathogenesis
• Prognosis
• KLK7
• KLK10