Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2018; 24(30): 3426-3439
Published online Aug 14, 2018. doi: 10.3748/wjg.v24.i30.3426
Identification of a five-long non-coding RNA signature to improve the prognosis prediction for patients with hepatocellular carcinoma
Qiu-Jie Zhao, Jiao Zhang, Lin Xu, Fang-Feng Liu
Qiu-Jie Zhao, Jiao Zhang, Lin Xu, Department of Gastroenterology, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, Shandong Province, China
Fang-Feng Liu, Department of Hepatobiliary Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, Shandong Province, China
Author contributions: Zhao QJ conceived the study, drafted and revised the manuscript; Zhang J and Xu L helped with the statistical analysis; Liu FF helped participated in data mining; all authors read and approved the final manuscript.
Supported by the National Nature Science Foundation of China, No. 81702816 (to Zhao QJ); and Shandong Provincial Natural Science Foundation, No. ZR2017PH030 (to Zhao QJ).
Institutional review board statement: This studied mined the TCGA database and doesn’t involve any experiments with animals or human beings. Because the TCGA data are a community resource project, additional ethical approval was not acquired.
Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.
Data sharing statement: The datasets supporting the conclusions of this article are included within the article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Qiu-Jie Zhao, PhD, Chief Doctor, Department of Gastroenterology, Shandong Provincial Hospital affiliated to Shandong University, No. 324, Jingwuwei 7th Road, Jinan 250021, Shandong Province, China.
Telephone: +86-531-68772952
Received: March 27, 2018
Peer-review started: March 28, 2018
First decision: May 9, 2018
Revised: May 24, 2018
Accepted: June 22, 2018
Article in press: June 22, 2018
Published online: August 14, 2018

To construct a long non-coding RNA (lncRNA) signature for predicting hepatocellular carcinoma (HCC) prognosis with high efficiency.


Differentially expressed lncRNAs (DELs) between HCC specimens and peritumor liver specimens were identified using the edgeR package to analyze The Cancer Genome Atlas (TCGA) LIHC dataset. Univariate Cox proportional hazards regression was performed to obtain the DELs significantly associated with overall survival (OS) in a training set. These OS-related DELs were further analyzed using a stepwise multivariate Cox regression model. Those lncRNAs fitted in the multivariate Cox regression model and independently associated with overall survival were chosen to build a prognostic risk formula. The prognostic value of this formula was then validated in the test group and the entire cohort and further compared with two previously identified prognostic signatures for HCC. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the potential biological functions of the lncRNAs in the signature.


Based on lncRNA expression profiling of 370 HCC patients from the TCGA database, we constructed a 5-lncRNA signature (AC015908.3, AC091057.3, TMCC1-AS1, DCST1-AS1 and FOXD2-AS1) that was significantly associated with prognosis. HCC patients with high-risk scores based on the expression of the 5 lncRNAs had significantly shorter survival times compared to patients with low-risk scores in both the training and test groups. Multivariate Cox regression analysis demonstrated that the prognostic value of the 5 lncRNAs was independent of clinicopathological parameters. A comparison study involving two previously identified prognostic signatures for HCC demonstrated that this 5-lncRNA signature showed improved prognostic power compared with the other two signatures. Functional enrichment analysis indicated that the 5 lncRNAs were potentially involved in metabolic processes, fibrinolysis and complement activation.


Our present study constructed a 5-lncRNA signature that improves survival prediction and can be used as a prognostic biomarker for HCC patients.

Keywords: Long non-coding RNA, Hepatocellular carcinoma, Prognosis, Survival prediction, Prognostic biomarker

Core tip: In the present study, we developed a 5-long non-coding RNA (lncRNA) signature for predicting the prognosis of hepatocellular carcinoma (HCC) patients based on The Cancer Genome Atlas database. The signature was reproducible and robust in another independent large-scale HCC cohort, supporting its utility and effectiveness. In addition, the prognostic value of the 5-lncRNA signature was independent of clinicopathological variables. When compared with two previously identified signatures for HCC survival prediction, this 5-lncRNA signature showed superior prognostic power. Our study indicates that the 5-lncRNA signature could improve survival prediction and could be used as a prognostic biomarker for HCC patients.