Identification of a competing endogenous RNA network associated with prognosis of pancreatic adenocarcinoma
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Cancer Cell International Open Access
RESEARCH
Identification of a competing endogenous RNA network associated with prognosis of pancreatic adenocarcinoma Wanqing Weng1,2†, Zhongjing Zhang1†, Weiguo Huang1, Xiangxiang Xu1, Boda Wu1,2, Tingbo Ye1, Yunfeng Shan3*, Keqing Shi1,2* and Zhuo Lin4*
Abstract Background: Emerging evidence suggests that competing endogenous RNAs plays a crucial role in the development and progress of pancreatic adenocarcinoma (PAAD). The objective was to identify a new lncRNA-miRNA-mRNA network as prognostic markers, and develop and validate a multi-mRNAs-based classifier for predicting overall survival (OS) in PAAD. Methods: Data on pancreatic RNA expression and clinical information of 445 PAAD patients and 328 normal subjects were downloaded from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Genotype-Tissue Expression (GTEx). The weighted correlation network analysis (WGCNA) was used to analyze long non-coding RNA (lncRNA) and mRNA, clustering genes with similar expression patterns. MiRcode was used to predict the sponge microRNAs (miRNAs) corresponding to lncRNAs. The downstream targeted mRNAs of miRNAs were identified by starBase, miRDB, miRTarBase and Targetscan. A multi-mRNAs-based classifier was develop using least absolute shrinkage and selection operator method (LASSO) COX regression model, which was tested in an independent validation cohort. Results: A lncRNA-miRNA-mRNA co-expression network which consisted of 60 lncRNAs, 3 miRNAs and 3 mRNAs associated with the prognosis of patients with PAAD was established. In addition, we constructed a 14-mRNAs-based classifier based on a training cohort composed of 178 PAAD patients, of which the area under receiver operating characteristic (AUC) in predicting 1-year, 3-year, and 5-year OS was 0.719, 0.806 and 0.794, respectively. The classifier also shown good prediction function in independent verification cohorts, with the AUC of 0.604, 0.639 and 0.607, respectively. Conclusions: A novel competitive endogenous RNA (ceRNA) network associated with progression of PAAD could be used as a reference for future molecular biology research. *Correspondence: [email protected]; [email protected]; [email protected] † Wanqing Weng and Zhongjing Zhang are first authors 2 Precision Medicine Center Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, People’s Republic of China 3 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, People’s Republic of China 4 Department of Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, People’s Republic of China Full list of author information is available at the end of the article © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give
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