Integrated analysis of Helicobacter pylori-related prognostic gene modification patterns in the tumour microenvironment of gastric cancer.

BACKGROUND

(HP) infection is one of the leading causes of gastric cancer (GC). However, the interaction between HP and the TME, and its carcinogenic mechanism remains unknown.

METHODS

The HP-related prognostic genes were identified based on HP infection-related gene markers and HP infection sample datasets by risk method and NMF algorithm. Principal component analysis (PCA) algorithm was used to constructed the HPscore system. The "limma" R package was employed to determine differentially expressed genes. In addition, the R packages, such as "xCell" and "GSVA", was used to analyze the relationship between the HPscore and tumor microenvironment. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to verify the expression levels of 28 HP-related prognostic genes in tissues.

RESULTS

We successfully identified 28 HP-related prognostic genes that accurately classified the GC population. There are significant differences in survival between different subgroups (high-, low-risk and cluster_1,2). Thereafter, the HPscore system was constructed to evaluate the signatures of the 28 HP-related prognostic genes. The overall survival rate in the high-HPscore group was poor and immunological surveillance was reduced, whereas the low-HPscore group had a survival advantage and was related to the inflammatory response. HPscore was also strongly correlated with the tumour stage, TME cell infiltration and stemness. The qRT-PCR results showed that DOCK4 expression level of 28 HP-related prognostic genes was higher in gastric cancer tissues than in adjacent tissues.

CONCLUSIONS

HP signatures play a crucial role in the TME and tumourigenesis. HPscore evaluation of a single tumour sample can help identify the TME characteristics and the carcinogenic mechanism of GC patients infected with HP, based on which personalized treatment can be administered.