Analysis of key genes and signaling pathways involved in Helicobacter pylori-associated gastric cancer based on The Cancer Genome Atlas database and RNA sequencing data

Abstract

Background: Helicobacter pylori (H. pylori) infection is associated with the development of gastric cancer, although the mechanism is unclear. Herein, this study aimed to clarify the key genes and signaling pathways involved in H. pylori pathogenesis based on The Cancer Genome Atlas (TCGA) database and RNA sequencing analysis.

Materials and methods: Forty-nine gastric cancer samples (16 with H. pylori and 33 without H. pylori) and 35 cancer-adjacent normal samples from TCGA database were analyzed by bioinformatics. The differentially expressed genes between H. pylori-positive and H. pylori-negative patients were verified in 18 gastric cancer (GC) samples (9 with H. pylori and 9 without H. pylori), which were analyzed using RNA sequencing. Survival analysis was carried out to explore associations between the differentially expressed genes and prognosis. Bioinformatics analysis was performed to determine the signaling pathways associated with H. pylori.

Results: The baseline level of clinical features from TCGA database and RNA sequencing showed no differences between the H. pylori-positive and H. pylori-negative GC groups (P > 0.05). TP53 was shown to be upregulated in the H. pylori-positive group in both TCGA database and RNA sequencing data, which also showed higher expression in the GC tissues than in adjacent normal tissues (P < 0.05). CCDC151, CHRNB2, GMPR2, HDGFRP2, and VSTM2L were shown to be downregulated in the H. pylori-positive group by both TCGA database and RNA sequencing, which also showed lower expression in the GC tissues than in adjacent normal tissues (P < 0.05). GC patients with low expression levels of HDGFRP2 had a poor prognosis (P < 0.05). Thirty-three signaling pathways and 10 biological processes were found to be positively associated with H. pylori infection (P < 0.05, FDR < 0.05).

Conclusions: These results indicate that some genes (TP53, CCDC151, CHRNB2, GMPR2, HDGFRP2, VSTM2L) and previously unidentified signaling pathways (eg, the Hippo signaling pathway) might play an important role in H. pylori-associated GC.

Keywords: Helicobacter pylori; RNA sequencing; TCGA; bioinformatics analysis; gastric cancer.