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Comprehensive investigation of key biomarkers and pathways in hepatitis B virus-related hepatocellular carcinoma
Guangxi Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Shuang Yong Rd 6, Nanning 530021, Guangxi Zhuang, Peoples R China..
Guangxi Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Shuang Yong Rd 6, Nanning 530021, Guangxi Zhuang, Peoples R China..
Guangxi Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Shuang Yong Rd 6, Nanning 530021, Guangxi Zhuang, Peoples R China..
Guangxi Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Shuang Yong Rd 6, Nanning 530021, Guangxi Zhuang, Peoples R China..
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2019 (English)In: Journal of Cancer, ISSN 1837-9664, E-ISSN 1837-9664, Vol. 10, no 23, p. 5689-5704Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
IVYSPRING INT PUBL , 2019. Vol. 10, no 23, p. 5689-5704
Keywords [en]
hepatitis B virus, hepatocellular carcinoma, DNA topoisomerase II alpha, protein regulator of cytokinesis 1, prognosis
National Category
Bioinformatics and Systems Biology
Identifiers
URN: urn:nbn:se:kth:diva-263405DOI: 10.7150/jca.31287ISI: 000490321900010Scopus ID: 2-s2.0-85074342463OAI: oai:DiVA.org:kth-263405DiVA, id: diva2:1368537
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20191107

Available from: 2019-11-07 Created: 2019-11-07 Last updated: 2020-02-04Bibliographically approved

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Liu, Zhengtao

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