A Prognostic Riskscore Model Related to Helicobacter pylori Infection in Stomach Adenocarcinoma

Abstract

Background: Helicobacter pylori (HP) is associated with the development of various stomach diseases, one of the major risk factors for stomach adenocarcinoma (STAD).

Methods: The HP infection score between tumor and normal groups was compared by single-sample gene set enrichment analysis (ssGSEA). The key modules related to HP infection were identified by weighted gene coexpression network analysis (WGCNA), and functional enrichment analysis was conducted on these module genes. Further, the limma package was used to screen the differentially expressed genes (DEGs) between HP-positive and HP-negative STAD. The prognostic genes were obtained to construct the riskscore model, and the performance of the model was validated. The correlation between riskscore and tumor immune microenvironment (TIME) was analyzed by Spearman’s method. The single-cell atlas of HP-positive STAD was delineated. The mRNA expression levels of the prognostic genes were verified using STAD cells, and the migration and invasion capacities of STAD cells were evaluated by using the wound healing assay and transwell assay.

Results: The HP infection score in the tumor group was significantly higher than that in the normal group. The purple and royal blue modules showed higher correlation with HP infection in STAD, and these module genes were enriched in the immune-related pathway. Further, five prognostic genes (CTLA4, CPVL, EMB, CXCR4, and FAM241A) were screened from the HP infection–related DEGs, which were utilized for establishing the riskscore model, with good robustness. Riskscore exhibited strong correlation with TIME in STAD. Single-cell atlas of HP-positive STAD revealed that CXCR4 is highly expressed in Epithelial Cell 1, Epithelial Cell 2, and parietal cells of the tumor group. CPVL, EMB, CTLA4, FAM241A, and CXCR4 showed high expression in STAD cells, and the silencing of CPVL could suppress the migration and invasion of STAD cells.

Conclusion: This study established a riskscore model based on HP infection–related genes, which could provide reference for prognostic prediction and treatment targets of STAD.