Analysis Of The Prognostic Biomarkers Associated With Cancer Stem Cell Characteristics And Immune Infiltration Of Helicobacter Pylori-induced Gastric Cancer

Objective:China is a country with a high incidence of gastric cancer,accounting for about half of the new cases in the world every year.The development of Gastric cancer(GC)is closely related to Helicobacter pylori(H.pylori)infection.Cancer stem cells(CSCs)play important roles in the survival,proliferation,metastasis and recurrence of tumors.However,the mechanism of CSCs and H.pylori-induced GC remains unclear.At the same time,the effect of tumor microenvironment on tumor stem cells and GC with H.pylori infection is also worth exploring.On the basis of the existing research on GC,it is still of great significance to further understand and explore the pathogenesis of GC through bioinformatics analysis.Methods:In order to explore the key genes influencing the stemness characteristics of GC,RNA-seq data and related clinical information of 408 GC samples and 30normal samples from the Cancer Genome Atlas Database(TCGA).m RNA expression-based stemness index,m RNAsi(m RNAsi)was adjusted for tumor purity,and then the correlation between m RNAsi and the clinical features(including tumor depth,pathological stage,and survival status)of GC associated with H.pylori infection was analyzed.Weighted gene coexpression network analysis(WGCNA)was used to identify the important modules and key genes related to m RNAsi,and the function and enrichment of the key genes were analyzed.A series of expression validations of key genes were performed via databases such as Oncomine and GEPIA.Kaplan-Meier database was used to explore the influence of lymph node metastasis on key genes and clinical prognosis of GC.Finally,the expression of key genes and the process of GC immune invasion were explored by TIMER and GEPIA.Results:1.There was higher m RNA expression-based stemness index(m RNAsi)in H.pylori(+)GC tumor tissue than in normal tissue.The clinical features of stage T and N were highly correlated with m RNAsi.2.The purple module was the most significant modules related to the m RNAsi by WGCNA and its key genes played played a major function related to tumor immunity,mainly involved in regulating the Jak-STAT signal pathway,Th17 cell differentiation pathway,and so on.3.These key genes were correlated with the high level of immune infiltration of CD8~+T cells,CD4~+T cells,macrophages,neutrophils and dendritic cells in GC via Tumor Immune Estimation Resource(TIMER).28 genes were found to be closely related to the characteristics of gastric CSCs(GCSCs)associated with H.pylori infection.13 genes were associated with lymph node metastasis in GC,which may lead to poor prognosis in patients.Conclusion:The characteristics of GCSCs were related to the interleukins signaling,cytokine signaling,Jak-STAT signaling pathway,which provides a new idea for screening therapeutic targets to inhibit the characteristics of GCSCs and a basis for the eradication of H.pylori and the prevention of GC.