Transcriptome Sequencing Identifies Key Pathways And Genes Involved In Gastric Adenocarcinoma

BackgroundGastric cancer,originated from the gastric mucosal epithelium,is one of the most common malignant tumors in the world.The mortality rate of gastric cancer ranks 2th in malignant tumors,and the incidence rate ranks 4th throughout the world.Gastric cancer includes many histological types and gastric adenocarcinoma is the most common.China has a high incidence of gastric cancer,with about 350000 deaths and 400000 new cases each year,accounting for about 40%of the gastric cancer cases around the world.Since there are few symptoms for early gastric cancer,the patients are usually diagnosed with advanced gastric cancers that are difficult to cure.For advanced gastric cancer,the 5-year survival rate is still less than 30%,even after comprehensive treatment based on surgery,which may be due to the lack of specific markers used for early diagnosis and detection of gastric cancer.Transcriptomics is a discipline that studies the structure,type,and function of all transcripts and transcriptional regulation in a certain cell at a certain time on a holistic level,and it can completely and quickly obtain the expression of a specific tissue or cell in a certain state.Transcriptomic analysis may provide a new direction for the early diagnosis of gastric cancer and the study of specific markers.ObjectiveWe aimed to investigate the key pathways,genes and miRNAs associated with gastric adenocarcinoma via transcriptome sequencing.MethodsFive pairs of gastric adenocarcinoma tissue and normal tissue were harvested.After sequencing,raw data were processed,and differentially expressed genes(DEGs)between tumor and control groups were screened,followed by functional enrichment analysis,gene clustering analysis and miRNA-target genes network.The effect of DEGs on patient prognosis was analyzed based on the survival data from gastric adenocarcinoma patients in The Cancer Genome Atlas database.Several genes were validated through real-time PCR.ResultsIn total,1477 upregulated and 282 downregulated DEGs were screened in tumor groups,compared with the control.These genes were segregated into four clusters:genes in cluster 1 were significantly involved in metabolism of xenobiotics by cytochrome P450;cluster 2,majorly involved in apoptosis,tight junction formation,and platelet activation;cluster 3,primarily enriched in the p53 signaling pathway;cluster 4,significantly enriched in the insulin resistance pathway.Furthermore,15 DEGs significantly influenced prognosis,such asF2R,CTHRC1,and RASGRP3.The expression levels of CYP2B6,MAPK13,CTHRC,RASGRP3 and PYGM were consistent with our analysis results.In addition,miR-506 targeted28 genes in cluster 2,and miR-26A and miR-26B targeted 15 genes in cluster3.ConclusionsThe pathways of metabolism of xenobiotics via cytochrome P450,apoptosis,tight junction formation,platelet activation,and insulin resistance may play important roles in the progression of gastric adenocarcinoma.CTHRC1 and RASGRP3 may serve as key prognostic markers.In addition,miR-506,miR-26A and miR-26B may play key roles in the development of gastric adenocarcinoma.