J Cancer 2019; 10(25):6298-6313. doi:10.7150/jca.33250

Research Paper

Genome-wide analysis to identify a novel microRNA signature that predicts survival in patients with stomach adenocarcinoma

Shan-Shan Luo1✉, Xi-Wen Liao2, Xiao-Dong Zhu3

1. Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
2. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
3. Department of Radiation Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.

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Citation:
Luo SS, Liao XW, Zhu XD. Genome-wide analysis to identify a novel microRNA signature that predicts survival in patients with stomach adenocarcinoma. J Cancer 2019; 10(25):6298-6313. doi:10.7150/jca.33250. Available from http://www.jcancer.org/v10p6298.htm

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Abstract

Objective: Using genome-wide screening, this study was aimed at identifying prognostic microRNA (miRNA) in those patients suffering from stomach adenocarcinoma (STAD).

Methods: A genome-wide miRNA sequencing dataset and relevant STAD clinical information was obtained via The Cancer Genome Atlas (TCGA). Prognostic miRNA selection was carried out through a whole genome multivariate Cox regression model in order to establish a prognostic STAD signature.

Results: Eleven miRNAs (hsa-mir-509-2, hsa-mir-3917, hsa-mir-495, hsa-mir-653, hsa-mir-3605, hsa-mir-2115, hsa-mir-1292, hsa-mir-137, hsa-mir-6511b-1, hsa-mir-145, and hsa-mir-138-2) were recognized as prognostic and used for the construction of a STAD prognostic signature. This signature exhibited good performance in predicting prognosis (adjusted P<0.0001, adjusted hazard ratio= 3.047, and 95% confidence interval=2.148-4.323). The time-dependent receiver operating characteristic examination exhibited area under curve values of 0.711, 0.697, 0.716, 0.733, 0.805, and 0.805, for 1-, 2-, 3-, 4-, 5-, and 10-year overall survival (OS) estimation, respectively. Comprehensive survival analysis suggests that the 11-miRNA prognostic signature acts as an independent feature of STAD prognosis and exhibits superior performance in OS prediction when compared to traditional clinical parameters. Furthermore, fourteen miRNA target genes were linked to STAD OS. These included SERPINE1, MLEC, ANGPT2, C5orf38, FZD7, MARCKS, PDGFD, DUSP6, IRS1, PSAT1, TENM3, TMEM127, BLMH, and TIRAP. Functional and gene set enrichment analysis suggested that target genes and the 11-miRNA prognostic signature were both participate in various biological processes and pathways, including the growth factor beta, Wnt, and Notch signaling pathways.

Conclusions: By means of a genome-wide analysis, an 11-miRNA expression signature that may serve as an underlying prognostic indicator for those patients suffering from STAD has been identified and described here.

Keywords: genome-wide, miRNA, TCGA, stomach adenocarcinoma, prognosis.