A Long Non-coding RNA Signature to Improve Prognostic Prediction of Pancreatic Ductal Adenocarcinoma

Chenhao Zhou; Shun Wang; Qiang Zhou; Jin Zhao; Xianghou Xia; Wanyong Chen; Yan Zheng; Min Xue; Feng Yang; Deliang Fu; Yirui Yin; Manar Atyah; Lunxiu Qin; Yue Zhao; Christiane Bruns; Huliang Jia; Ning Ren; Qiongzhu Dong

doi:10.3389/fonc.2019.01160

A Long Non-coding RNA Signature to Improve Prognostic Prediction of Pancreatic Ductal Adenocarcinoma

Front Oncol. 2019 Nov 8:9:1160. doi: 10.3389/fonc.2019.01160. eCollection 2019.

Authors

Chenhao Zhou¹, Shun Wang², Qiang Zhou¹, Jin Zhao², Xianghou Xia³, Wanyong Chen^{1

4}, Yan Zheng², Min Xue⁴, Feng Yang⁵, Deliang Fu⁵, Yirui Yin¹, Manar Atyah¹, Lunxiu Qin^{2

4}, Yue Zhao⁶, Christiane Bruns⁶, Huliang Jia², Ning Ren^{1

7}, Qiongzhu Dong^{2

4}

Affiliations

¹ Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
² Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China.
³ Department of Breast Surgery, Zhejiang Cancer Hospital, Zhejiang, China.
⁴ Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
⁵ Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Fudan University, Shanghai, China.
⁶ Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany.
⁷ Institute of Fudan Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China.

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive solid malignant tumors worldwide. Increasing investigations demonstrate that long non-coding RNAs (lncRNAs) expression is abnormally dysregulated in cancers. It is crucial to identify and predict the prognosis of patients for the selection of further therapeutic treatment. Methods: PDAC lncRNAs abundance profiles were used to establish a signature that could better predict the prognosis of PDAC patients. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied to establish a multi-lncRNA signature in the TCGA training cohort (N = 107). The signature was then validated in a TCGA validation cohort (N = 70) and another independent Fudan cohort (N = 46). Results: A five-lncRNA signature was constructed and it was significantly related to the overall survival (OS), either in the training or validation cohorts. Through the subgroup and Cox regression analyses, the signature was proven to be independent of other clinic-pathologic parameters. Receiver operating characteristic curve (ROC) analysis also indicated that our signature had a better predictive capacity of PDAC prognosis. Furthermore, ClueGO and CluePedia analyses showed that a number of cancer-related and drug response pathways were enriched in high risk groups. Conclusions: Identifying the five-lncRNA signature (RP11-159F24.5, RP11-744N12.2, RP11-388M20.1, RP11-356C4.5, CTC-459F4.9) may provide insight into personalized prognosis prediction and new therapies for PDAC patients.

Keywords: lncRNA; overall survival; pancreatic ductal adenocarcinoma; prognosis; signature.