Identification of dysregulated long noncoding RNA and associated mechanism in gastric cancer

Abstract BackgroundsGastric cancer (GC) is one of the most malignant epithelial tumors. The incidence of GC varies worldwide, and nearly half of the cases occur in Asian countries, especially in Japan and China. GC is the 3rd leading cause of cancer-related deaths in the world, and current prognosis of advanced GC remains dismal despite improvements in diagnosis and therapy. Our current study aimed to identify significant long noncoding RNAs with the prognostic potential and preliminarily to investigate the underlying mechanisms the identified long noncoding RNAs.MethodsWe retrieved articles reporting human LncRNA microarray in GC patients and pooled eligible studies for meta-analysis. GEO2R and Qigen’s IPA analysis was utilized for searching potential interacted molecules with differentially expressed LncRNA in GC. The expression of eligible LncRNA and molecules in GC were validated in public GC dataset by GEPIA website. And Kaplan Meier plots was employed to analyze the correlation between target molecules and prognosis of GC.ResultsThis study identified a variety of reports to investigate the expression of lncRNAs in GC development using high-throughput lncRNA detection. Eight of them were further verified with significant expression in GC tissues by using Gene Expression Profiling Interactive Analysis (GEPIA). Next, the molecular interactions with eight lncRNAs were further identified by using Qiagen’s IPA system. Simultaneously, differentially expressed genes (DEGs) of GC were also identified via the GEO2R online tool and datasets (GSE54129, GSE19826, and GSE79973). Finally, through Venn diagram analysis, our study found that IGF2BP3 and FOLR1 have strong relationship with lncRNAs H19 and PVT1 respectively in the background of stomach cancer. The expression of IGF2BP3 and FOLR1 in GC was further revealed to be correlate to a worsening prognosis for GC patients by Kaplan Meier plots. IGF2BP3 promotes the expression of H19 and PEG10, the down-regulation of which might improve the GC prognosis. FOLR1 is a crucial component of cell metabolism and DNA synthesis/repair required for cancer cell division. Currently, there is no evidence to report IGF2BP3 and FOLR1 to correlate to GC prognosis.ConclusionIn summary, using an integrated bioinformatic approach we identified eight lncRNAs with prognostic potential in GC patients and further revealed two axes - H19-IGF2BP3 and PVT1-FOLR1 – that might interpret the underlying mechanism involving in prognosis of GC and provide new insights into the etiology and management of GC patients.