Research Paper|Volume 13, Issue 2|pp 2959—2981

A novel five-lncRNA signature panel improves high-risk survival prediction in patients with cholangiocarcinoma

Xiaozai Xie^1,², Yi Wang³, Sina Zhang^3,⁴, Jialiang Li^1,², Zhengping Yu¹, Xiwei Ding⁵, Longyun Ye¹, Peirong Gong⁶, Qiandong Zhu¹, Junjian Li¹, Ziyan Chen⁷, Xinfei Yao⁷, Zhiyong Du⁸, Qiqiang Zeng^1,², Hanbin Chen⁹, Zhen Yang¹⁰, Gang Chen^1,²

¹Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
²Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
³Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China
⁴School of Public Health, Inner Mongolia Medical University, Hohhot, China
⁵Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
⁶Department of Hepatobiliary Surgery, The Affiliated Cixi Hospital of Wenzhou Medical University, Ningbo, China
⁷Division of Clinical Medicine, First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, China
⁸Department of Hepatobiliary Surgery, Shenzhen People’s Hospital, Shenzhen, China
⁹Department of Radiotherapy and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
¹⁰Department of Infectious Diseases, Shandong Provincial Hospital, Jinan, China

* Equal contribution

Received: June 19, 2020Accepted: November 23, 2020Published: January 20, 2021

https://doi.org/10.18632/aging.202446

Copyright: © 2021 Xie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Cholangiocarcinoma (CCA) is a fatal disease with dismal survival rates. Long non-coding RNA (lncRNA) expression profiling as potential prognostic biomarkers play critical roles in tumor initiation, development, and poor prognosis. Identifying specific lncRNA to predict the prognosis of CCA patients in the early stages is very important for improving a patient’s survival. In the current study, we aimed to establish a novel risk-stratification lncRNA signature panel in CCA. The initial lncRNA discovery was identified in The Cancer Genome Atlas database (TCGA cohort). The Cox regression analysis was used to establish the lncRNA prognostic model and the receiver operating characteristic (ROC) curve analysis was performed to assess the specificity and sensitivity of the model. This was followed by independent validation of the lncRNA signature in the CCA patients from the First Affiliated Hospital of Wenzhou Medical University (WMU cohort). Furthermore, by using the Gene Ontology function and Kyoto Encyclopedia Gene and Genome pathway enrichment analysis, we explored the potential function of prognosis lncRNA. Finally, five lncRNA (HULC; AL359715.5; AC006504.8; AC090114.2; AP00943.4) were screened to establish the predictive model that significantly associated with poor overall survival(HR:4.879;95%CI,1.587-14.996;p=0.006). This five-lncRNA signature model showed excellent accuracy in the TCGA cohort (AUC=0.938), and also robustly predicted survival in the validation WMU cohort(AUC=0.816). Functional enrichment analysis suggested prognostic lncRNA was primarily associated with CCA-related biological processes. Our data established a novel lncRNA signature model for CCA risk-stratification and robust identification of CCA patients with poor molecular genotypes. Moreover, it revealed new molecular mechanisms of CCA.