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Screening Of Prognostic Mirna Biomarkers For Gastric Cancer And Analysis Of Their Biological Function

Posted on:2019-08-31Degree:MasterType:Thesis
Country:ChinaCandidate:H H XiaoFull Text:PDF
GTID:2404330548491656Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
Objective: The purpose of this study is to identify specific mi RNA intimately associated with survival from differentially expressed mi RNA in gastric cancer as prognostic biomarkers.Method: Firstly,the mi RNA-seq data and corresponding clinical information of 394 gastric cancer patients were obtained from the Cancer Genome Atlas database,the differentially expressed mi RNA between the cancer and adjacent tissue were analyzed by using the edg R package of R language,and reliability of this analysis was verified by using q PCR.Subsequently,a linear prognostic model of mi RNA was constructed based on self-validation(randomly divided into two subgroups: 197 training samples and 197 testing samples)by using Cox proportional hazards model and supervised principal component analysis method,patients were divided into high-risk and low-risk groups according to the calculated prognostic score,and Time-dependent ROC curve was used to assess the performance of the model.Finally,the target genes of mi RNA in the prognosis model were predicted and its biological fuction were analyzed.Results: A total of 299 differentially expressed mi RNA,including 219 up-regulated mi RNA and 80 down-regulated mi RNA,were screened in this study,the results of q PCR validation on three randomly selected mi RNA(mi R-335-5p,has-mi R-21-5p,has-mi R-139-5p)were consistent with those of differential expression analysis.A linear prognostic model composed of 9-mi RNA(mi R-145,mi R-30 a,mi R-549 a,mi R-4746,mi R-708,mi R-5586,mi R-373,mi R-187,mi R-422a)was developed,Kaplan-Meier analysis demonstrated that patients in the high-risk group had worse overall survival compared with patients in the low-risk group.this prognostic model showed good prognostic significance to the gastric cancer patients in early stages and the chemotherapy patients,and notably,the 9-mi RNA is an independent prognostic factor for gastric cancer.A total of 8856 target genes were predicted,which are mainly enriched in the MAPK signaling pathway,Wnt signaling pathway,Erb B signaling pathway,Adherens junction signaling pathway,TGF-? signaling pathway and m TOR signaling pathway,etc.Conclusions: 1.9-mi RNA(mi R-145,mi R-30 a,mi R-549 a,mi R-4746,mi R-708,mi R-5586,mi R-373,mi R-187,mi R-422a)is a potential prognostic biomarker and an independent prognostic factor for gastric cancer.2.The pathogenesis of gastric cancer may associate with MAPK signaling pathway,Wnt signaling pathway,Erb B signaling pathway,Adherens junction signaling pathway,TGF-? signaling pathway and m TOR signaling pathway,etc.
Keywords/Search Tags:Gastric cancer, The Cancer Genome Altas database, miRNA, Biomarker
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