J Cancer 2019; 10(23):5689-5704. doi:10.7150/jca.31287

Research Paper

Comprehensive investigation of key biomarkers and pathways in hepatitis B virus-related hepatocellular carcinoma

Xiwen Liao1, Tingdong Yu1, Chengkun Yang1, Ketuan Huang1, Xiangkun Wang1, Chuangye Han1, Rui Huang2, Xiaoguang Liu1,3, Long Yu1,4, Guangzhi Zhu1, Hao Su1, Wei Qin1, Jianlong Deng1,5, Xianmin Zeng1, Bowen Han1, Quanfa Han1, Zhengqian Liu1, Xin Zhou1, Junqi Liu1, Yizhen Gong6,7, Zhengtao Liu1,8,9, Jianlv Huang1,10, Lei Lu1,11, 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 Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
3. Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong Province, China;
4. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan Province, China;
5. Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital of Guangxi Medical University, Yulin, 537000, Guangxi Zhuang Autonomous Region, People's Republic of 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. Department of General Surgery, Beijing Haidian Hospital, Beijing Haidian Section of Peking University Third Hospital, Beijing, 100080, People's Republic of China.

Abstract

Objective: Our study is aim to explore potential key biomarkers and pathways in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) using genome-wide expression profile dataset and methods.

Methods: Dataset from the GSE14520 is used as the training cohort and The Cancer Genome Atlas dataset as the validation cohort. Differentially expressed genes (DEGs) screening were performed by the limma package. Gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), gene ontology, the Kyoto Encyclopedia of Genes and Genomes, and risk score model were used for pathway and genes identification.

Results: GSEA revealed that several pathways and biological processes are associated with hepatocarcinogenesis, such as the cell cycle, DNA repair, and p53 pathway. A total of 160 DEGs were identified. The enriched functions and pathways of the DEGs included toxic substance decomposition and metabolism processes, and the P450 and p53 pathways. Eleven of the DEGs were identified as hub DEGs in the WGCNA. In survival analysis of hub DEGs, high expression of PRC1 and TOP2A were significantly associated with poor clinical outcome of HBV-related HCC, and shown a good performance in HBV-related HCC diagnosis. The prognostic signature consisting of PRC1 and TOP2A also doing well in the prediction of HBV-related HCC prognosis. The diagnostic and prognostic values of PRC1 and TOP2A was confirmed in TCGA HCC patients.

Conclusions: Key biomarkers and pathways identified in the present study may enhance the comprehend of the molecular mechanisms underlying hepatocarcinogenesis. Additionally, mRNA expression of PRC1 and TOP2A may serve as potential diagnostic and prognostic biomarkers for HBV-related HCC.

Keywords: hepatitis B virus, hepatocellular carcinoma, DNA topoisomerase II alpha, protein regulator of cytokinesis 1, prognosis

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How to cite this article:
Liao X, Yu T, Yang C, Huang K, Wang X, Han C, Huang R, Liu X, Yu L, Zhu G, Su H, Qin W, Deng J, Zeng X, Han B, Han Q, Liu Z, Zhou X, Liu J, Gong Y, Liu Z, Huang J, Lu L, Ye X, Peng T. Comprehensive investigation of key biomarkers and pathways in hepatitis B virus-related hepatocellular carcinoma. J Cancer 2019; 10(23):5689-5704. doi:10.7150/jca.31287. Available from http://www.jcancer.org/v10p5689.htm