A Five-microRNA Signature for Survival Prognosis in Pancreatic Adenocarcinoma based on TCGA Data

Abstract

Novel biomarkers for pancreatic adenocarcinoma are urgently needed because of its poor prognosis. Here, by using The Cancer Genome Atlas (TCGA) RNA-seq data, we evaluated the prognostic values of the differentially expressed miRNAs and constructed a five-miRNA signature that could effectively predict patient overall survival (OS). The Kaplan-Meier overall survival curves of two groups based on the five miRNAs were notably different, showing overall survival in 10.2% and 47.8% at five years for patients in high-risk and low-risk groups, respectively. The ROC curve analysis achieved AUC of 0.775, showing good sensitivity and specificity of the five-miRNA signature model in predicting pancreatic adenocarcinoma patient survival risk. The functional enrichment analysis suggested that the target genes of the miRNA signature may be involved in various pathways related to cancer, including PI3K-Akt, TGF-β, and pluripotent stem cell signaling pathways. Finally, we analyzed expression of the five specific miRNAs in the miRNA signature, and validated the reliability of the results in 20 newly diagnosed pancreatic adenocarcinoma patients using qRT-PCR. The expression results of qRT-PCR were consistent with the TCGA results. Taken together, these findings suggested that the five-miRNA signature (hsa-miR-203, hsa-miR-424, hsa-miR-1266 hsa-miR-1293, and hsa-miR-4772) could be used as a prognostic marker for pancreatic adenocarcinoma.

Prognostic and predictive factors in pancreatic cancer

“…Interestingly, the miRNA 200s family has been shown to suppressor tumor progression via EMT inhibition [50]. More recently, a number of multigene prognostic signatures have been proposed, of 2 [51], 5 [52] or 11 microRNAs [53].…”

Identification of a robust functional subpathway signature for pancreatic ductal adenocarcinoma by comprehensive and integrated analyses

“…Until now, 11 studies on the identification of gene signatures in PDAC have been published (Birnbaum, et al, 2017;Chen, et al, 2015;Haider, et al, 2014;Kirby, et al, 2016;Ma, et al, 2011;Newhook, et al, 2014;Raman, et al, 2018;Shi, et al, 2017;Shi, et al, 2018;Stratford, et al, 2010;Wang, et al, 2013). By using multivariate Cox methods, we retrospectively analyzed the predictive capacity of each of them on the present 11 datasets and found that these gene signatures were less robust than the path:00982_1 signature ( Supplementary Table S3).…”

“…PDAC has a complex molecular landscape (Raphael BJ, 2017). Efforts in identifying PDAC datasets have led to the discovery of potential gene signatures, which contain various numbers of distinguishable genes (Birnbaum, et al, 2017;Chen, et al, 2015;Haider, et al, 2014;Kirby, et al, 2016;Ma, et al, 2011;Newhook, et al, 2014;Raman, et al, 2018;Shi, et al, 2017;Shi, et al, 2018;Stratford, et al, 2010;Wang, et al, 2013). However, these reported signatures have few overlapping component genes with different functions, raising questions about their biological relevance, clinical significance and universal application for the management of PDAC.…”

Identification of a robust functional subpathway signature for pancreatic ductal adenocarcinoma by comprehensive and integrated analyses

“…Until now, 11 studies on the identification of gene signatures in PDAC have been published [6][7][8][9][10][11][12][13][14][15][16]. By using multivariate Cox methods, we retrospectively analyzed the predictive capacity of these signatures in the present 11 datasets, in comparison with the path:00982_1 signature.…”

“…PDAC has a very complex molecular landscape [5]. Efforts in deeply analyzing datasets have led to the discovery of potential PDAC gene signatures, which contain various numbers of distinguishable genes [6][7][8][9][10][11][12][13][14][15][16]. However, these reported signatures have few overlapping component genes with different functions, raising questions about their biological relevance, clinical significance and universal application for the management of PDAC.…”