Prediction of novel biomarkers for gastric intestinal metaplasia and gastric adenocarcinoma using bioinformatics analysis

Highlights•ECM interaction in GC and PPAR signaling pathway interaction in intestinal metaplasia may play key roles in the progression of GC.•COL1A2, COL4A1, and COL6A3 were significantly correlated with overexpression, poor prognosis, and the highest mutation rates in GC.•FABP1, APOC3, APOA1, HMGCS2, PPARA, and PCK1 are important biomarkers that have received little attention in IM.•Developing and forecasting the GC via regulating the hub genes may be affected by hsa-miR-29.AbstractBackground & aimThe histologic and molecular changes from intestinal metaplasia (IM) to gastric cancer (GC) have not been fully characterized. The present study sought to identify potential alterations in signaling pathways in IM and GC to predict disease progression; these alterations can be considered therapeutic targets.Materials & methodsSeven gene expression profiles were selected from the GEO database. Discriminate differentially expressed genes (DEGs) were analyzed by EnrichR. The STRING database, Cytoscape, Gene Expression Profiling Interactive Analysis (GEPIA), cBioPortal, NetworkAnalyst, MirWalk database, OncomiR, and bipartite miRNA‒mRNA correlation network was used for downstream analyses of selected module genes.ResultsAnalyses revealed that extracellular matrix-receptor interactions (ITGB1, COL1A1, COL1A2, COL4A1, FN1, COL6A3, and THBS2) in GC and PPAR signaling pathway interactions (FABP1, APOC3, APOA1, HMGCS2, and PPARA and PCK1) in IM may play key roles in both the carcinogenesis and progression of underlying GC from intestinal metaplasia. IM enrichment indicated that this is closely related to digestion and absorption. The TF-hub gene regulatory network revealed that AR, TCF4, SALL4, and ESR1 were more important for hub gene expression. It was revealed that the development and prediction of GC may be affected by hsa-miR-29. It was found that PTGR1, C1orf115, CRYL1, ALDOB, and SULT1B1 were downregulated in GC and upregulated in IM. Therefore, they might have tumor suppressor activity in GC progression.ConclusionNew potential biomarkers and pathways involved in GC and IM were identified that are important for the transformation of GC from IM to adenocarcinoma and can be therapeutic targets for GC.