Genome-scale analysis to identify prognostic microRNA biomarkers in patients with early stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy
Received 15 March 2018
Accepted for publication 14 May 2018
Published 10 August 2018 Volume 2018:10 Pages 2537—2551
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 4
Editor who approved publication: Dr Kenan Onel
Xiwen Liao,1 Xiangkun Wang,1 Ketuan Huang,1 Chengkun Yang,1 Tingdong Yu,1 Chuangye Han,1 Guangzhi Zhu,1 Hao Su,1 Rui Huang,2 Tao Peng1
1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
Background: The aim of the study was to investigate potential prognostic microRNA (miRNA) biomarkers for patients with early stage pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using a miRNA-sequencing (miRNA-seq) data set from The Cancer Genome Atlas (TCGA). A miRNA expression-based prognostic signature was generated, and the potential role of target genes in overall survival (OS) in patients with PDAC was examined.
Methods: A miRNA-seq data set of 112 PDAC patients who underwent pancreaticoduodenectomy was obtained from TCGA. Survival analysis was performed to identify potential prognostic biomarkers.
Results: Eleven miRNAs (hsa-mir-501, hsa-mir-4521, hsa-mir-5091, hsa-mir-24-1, hsa-mir-126, hsa-mir-30e, hsa-mir-3157, hsa-let-7a-3, hsa-mir-133a-1, hsa-mir-4709, and hsa-mir-421) were used to construct a prognostic signature using the step function. The 11-miRNA prognostic signature showed good performance for prognosis prediction (adjusted P<0.0001, adjusted hazard ratio =4.285, 95% confidence interval =2.146–8.554), and the time-dependent receiver operating characteristic analysis showed an area under the curve of 0.864, 0.877, and 0.787 for 1-, 2-, and 3-year PDAC OS predictions, respectively. Comprehensive survival analysis suggested that the prognostic signature could serve as an independent prognostic factor for PDAC OS and performs better in prognosis prediction than other traditional clinical indicators. Functional assessment of the target genes of the miRNAs indicated that they were significantly enriched in multiple biological processes and pathways, including cell proliferation, cell cycle biological processes, the forkhead box O, mitogen-activated protein kinase, Janus kinase/signal transducers and activators of transcription signaling pathways, pathways in cancer, and the ErbB signaling pathway. Several target genes of these miRNAs were also associated with PDAC OS.
Conclusion: The present study identified a novel miRNA expression signature that showed potential as a prognostic biomarker for PDAC after pancreaticoduodenectomy.
Keywords: microRNA, prognosis, pancreatic ductal adenocarcinoma, TCGA, pancreaticoduodenectomy
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