Differentially Expressed mRNAs and Their Long Noncoding RNA Regulatory Network with Helicobacter pylori-Associated Diseases including Atrophic Gastritis and Gastric Cancer

Abstract EN

Background.

Helicobacter pylori (Hp) infection is the strongest risk factor for gastric cancer (GC).

However, the mechanisms of Hp-associated GC remain to be explored.

Methods.

The gene expression profiling (GSE111762) data were downloaded from the GEO database.

Differentially expressed genes (DEGs) between normal samples (NO) and Hp-atrophic gastritis (GA) or Hp-GA and Hp-GC were identified by GEO2R.

Gene Ontology and pathway enrichment analysis were performed using the DAVID database.

lncRNA-TF-mRNA and ceRNA regulation networks were constructed using Cytoscape.

The cross-networks were obtained by overlapping molecules of the above two networks.

GSE27411 and GSE116312 datasets were employed for validation.

Results.

DEGs between NO and Hp-GA are linked to the activity of inward rectifying potassium channels, digestion, etc.

DEGs between Hp-GA and Hp-GC were associated with digestion, positive regulation of cell proliferation, etc.

According to the lncRNA-TF-mRNA network, 63 lncRNAs, 12 TFs, and 209 mRNAs were involved in Hp-GA while 16 lncRNAs, 11 TFs, and 92 mRNAs were contained in the Hp-GC network.

In terms of the ceRNA network, 120 mRNAs, 18 miRNAs, and 27 lncRNAs were shown in Hp-GA while 72 mRNAs, 8 miRNAs, and 1 lncRNA were included in the Hp-GC network.

In the cross-network, we found that immune regulation and differentiation regulation were important in the process of NO-GA.

Neuroendocrine regulation was mainly related to the process of GA-GC.

In the end, we verified that CDX2 plays an important role in the pathological process of NO to Hp-GA.

Comparing Hp-GA with Hp-GC, DEGs (FPR1, TFF2, GAST, SST, FUT9, and SHH), TF, and GATA5 were of great significance.

Conclusions.

We identified the DEGs, and their lncRNA regulatory network of Hp-associated diseases might provide insights into the mechanism between Hp infection and GC.

Furthermore, in-depth studies of the molecules might be useful to explore the multistep process of gastric diseases.