Background Previous studies have indicated that chronic inflammation linked to H. pylori infection is the leading causes for gastric cancer (GC). However, the exact mechanism is not entirely clear until now. Purpose To identify the key molecules and TFs involved in H. pylori infection and to provide new insights into H. pylori-associated carcinogenesis and lay the groundwork for the prevention of GC. Results GO and KEGG analysis revealed that the DEGs of Hp+-NAG were mainly associated with the immune response, chemokine activity, extracellular region and rheumatoid arthritis pathway. The DEGs of Hp+-AG-IM were related to the apical plasma membrane, intestinal cholesterol absorption, transporter activity and fat digestion and absorption pathway. In Hp+-NAG network, the expression of TNF, CXCL8, MMP9, CXCL9, CXCL1, CCL20, CTLA4, CXCL2, C3, SAA1 and FOXP3, JUN had statistical significance between normal and cancer in TCGA database. In Hp+-AG-IM network the expression of APOA4, GCG, CYP3A4, XPNPEP2 and FOXP3, JUN were statistically different in the comparison of normal and cancer in TCGA database. FOXP3 were negatively associated with overall survival, and the association for JUN was positive. Conclusion The current study identified key DEGs and their transcriptional regulatory networks involved in H. pylori-associated NAG, AG-IM and GC and found that patients with higher expressed FOXP3 or lower expressed JUN had shorter overall survival time. Our study provided new directions for inflammation-associated oncogenic transformation involved in H. pylori infection.

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.

Background: Dysregulated expression of TRIB3 and FABP1 have been previously observed in human cancer tissues. However, there are little information as to their expression change in dynamic gastric diseases and the functional roles.Methods: Tissues from a total of 479 patients, including 89 GS, 102 IM-GA, 144 EGC, and 144 AGC were collected. The protein expressions of TRIB3 and FABP1 were detected by immunohistochemical staining. Meanwhile, the potential functions of TRIB3 and FABP1 in GC were further analyzed by R software and some internet public databases, such as TCGA and DAVID.Results: During this multi-stage process that go through GS to EGC, the expression trend of TRIB3 and FABP1 protein was GS > IM-GA > EGC. Besides, the expression of TRIB3 protein continued to decrease in AGC, while the expression of FABP1 was abnormally increased. Hp infection was significantly associated with the decreased expression of TRIB3 and FABP1. In addition, the diagnostic efficiency of the combination of these two indicators to diagnose EGC was higher than that of a single indicator. Survival analysis showed that higher expression of TRIB3 or FABP1 could indicate a better prognosis of GC. The protein expressions of TRIB3 and FABP1 were significantly positively correlated. Moreover, CEACAM5 and PRAP1 were positively correlated with both TRIB3 and FABP1 expressions, while GABRP and THBS4 were negatively correlated. The macrophages M0 infiltration was positively correlated with both TRIB3 and FABP1 expressions.Conclusion: The protein expressions of TRIB3 and FABP1 gradually decreased with the gastric disease progress, and was positively correlated. Hp infection may reduce the protein expression of TRIB3 and FABP1. Combing TRIB3 and FABP1 expressions can improve the diagnostic efficiency for EGC. Either a high expression of TRIB3 or FABP1 indicates a better prognosis for GC. TRIB3 and FABP1 may interact with CEACAM5, PRAP1, GABRP and THBS4, and affect tumor immune microenvironment by regulating immune cells, and participate in the development and progression of GC.