Journal
JOURNAL OF CANCER
Volume 10, Issue 23, Pages 5689-5704Publisher
IVYSPRING INT PUBL
DOI: 10.7150/jca.31287
Keywords
hepatitis B virus; hepatocellular carcinoma; DNA topoisomerase II alpha; protein regulator of cytokinesis 1; prognosis
Categories
Funding
- National Natural Science Foundation of China [81560535, 81802874, 81072321, 30760243, 30460143, 30560133]
- Natural Science Foundation of Guangxi Province of China [2018GXNSFBA138013, 2018GXNSFAA050119]
- 2009 Program for New Century Excellent Talents in University (NCET), Guangxi Natural Sciences Foundation [1104003A-7]
- Guangxi Health Ministry Medicine Grant (Key-Scientific Research) [Z201018]
- Scientific Research Fund of the Health and Family Planning Commission of Guangxi Zhuang Autonomous Region [Z2016318]
- project of Key laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education [GKE2018-01, GKE2019-11]
- The Guangxi Key RD Program [GKEAB18221019]
- Basic Ability Improvement Project for Middle-aged and Young Teachers in Colleges and Universities in Guangxi [2018KY0110]
- Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis [GXCDCKL201902]
- 2018 Innovation Project of Guangxi Graduate Education [JGY2018037, YCBZ2018036]
- Research Institute of Innovative Think-tank in Guangxi Medical University
- National Key Clinical Specialty Programs (General Surgery Oncology)
- Key Laboratory of Early Prevention & Treatment for Regional High-Incidence Tumor (Guangxi Medical University), Ministry of Education, China
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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.
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