J Cancer 2019; 10(14):3267-3283. doi:10.7150/jca.29986

Research Paper

Integrated analysis of competing endogenous RNA network revealing potential prognostic biomarkers of hepatocellular carcinoma

Xiwen Liao1, Xiangkun Wang1, Ketuan Huang1, Chuangye Han1, Jianlong Deng1,2, Tingdong Yu1, Chengkun Yang1, Rui Huang3, Xiaoguang Liu1,4, Long Yu1,5, Guangzhi Zhu1, Hao Su1, Wei Qin1, Xianmin Zeng1, Bowen Han1, Quanfa Han1, Zhengqian Liu1, Xin Zhou1, Yizhen Gong6,7, Zhengtao Liu1,8,9, Jianlv Huang1,10, Cheryl A Winkler11, Stephen J. O'Brien12,13, Xinping Ye1, Tao Peng1✉

1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
2. Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital of Guangxi Medical University, Yulin, 537000, Guangxi Zhuang Autonomous Region, People's Republic of China
3. Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
4. Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong Province, China;
5. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan Province, China;
6. Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
7. Department of Evidence-based Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
8. Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health and Key Laboratory of Organ Transplantation of Zhejiang Province, Hangzhou, 310003, Zhejiang Province, People's Republic of China.
9. Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, SE-171 21, Sweden.
10. Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530031, Guangxi Zhuang Autonomous Region, People's Republic of China.
11. Basic Research Laboratory, CCR, NCI and Leidos Biomedical Research, Frederick National Laboratory, Frederick MD. 21702, USA.
12. Theodosius Dobzhansky Center for Genome Bioinformatics, Saint-Petersburg State University, Saint-Petersburg, 199004, Russia.
13. Oceanographic Center, Nova Southeastern University, Ft Lauderdale, 33004, FL, USA.

Abstract

Objective: The goal of our study is to identify a competing endogenous RNA (ceRNA) network using dysregulated RNAs between HCC tumors and the adjacent normal liver tissues from The Cancer Genome Atlas (TCGA) datasets, and to investigate underlying prognostic indicators in hepatocellular carcinoma (HCC) patients.

Methods: All of the RNA- and miRNA-sequencing datasets of HCC were obtained from TCGA, and dysregulated RNAs between HCC tumors and the adjacent normal liver tissues were investigated by DESeq and edgeR algorithm. Survival analysis was used to confirm underlying prognostic indicators.

Results: In the present study, we constructed a ceRNA network based on 16 differentially expressed genes (DEGs), 7 differentially expressed microRNAs and 34 differentially expressed long non-coding RNAs (DELs). Among these dysregulated RNAs, three DELs (AP002478.1, HTR2A-AS1, and ERVMER61-1) and six DEGs (enhancer of zeste homolog 2 [EZH2], kinesin family member 23 [KIF23], chromobox 2 [CBX2], centrosomal protein 55 [CEP55], cell division cycle 25A [CDC25A], and claspin [CLSPN]) were used for construct a prognostic signature for HCC overall survival (OS), and performed well in HCC OS (adjusted P<0.0001, adjusted hazard ratio = 2.761, 95% confidence interval = 1.838-4.147). Comprehensive survival analysis demonstrated that this prognostic signature may be act as an independent prognostic indicator of HCC OS. Functional assessment of these dysregulated DEGs in the ceRNA network and gene set enrichment of this prognostic signature suggest that both were enriched in the biological processes and pathways of the cell cycle, cell division and cell proliferation.

Conclusions: Our current study constructed a ceRNA network for HCC, and developed a prognostic signature that may act as an independent indicator for HCC OS.

Keywords: competing endogenous RNA, hepatocellular carcinoma, bioinformatics, prognosis, TCGA.

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How to cite this article:
Liao X, Wang X, Huang K, Han C, Deng J, Yu T, Yang C, Huang R, Liu X, Yu L, Zhu G, Su H, Qin W, Zeng X, Han B, Han Q, Liu Z, Zhou X, Gong Y, Liu Z, Huang J, Winkler CA, O'Brien SJ, Ye X, Peng T. Integrated analysis of competing endogenous RNA network revealing potential prognostic biomarkers of hepatocellular carcinoma. J Cancer 2019; 10(14):3267-3283. doi:10.7150/jca.29986. Available from http://www.jcancer.org/v10p3267.htm