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Genetic variants and Expression of Cytochrome p450 Oxidoreductase Predict Postoperative Survival in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma
Guangxi Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Shuang Yong Rd 6, Nanning 530021, Guangxi, Peoples R China..
Guangxi Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Shuang Yong Rd 6, Nanning 530021, Guangxi, Peoples R China..
Guangxi Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Shuang Yong Rd 6, Nanning 530021, Guangxi, Peoples R China..
Guangxi Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Shuang Yong Rd 6, Nanning 530021, Guangxi, Peoples R China..
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2019 (English)In: Journal of Cancer, ISSN 1837-9664, E-ISSN 1837-9664, Vol. 10, no 6, p. 1453-1465Article in journal (Refereed) Published
Abstract [en]

Our current study investigates the prognostic values of genetic variants and mRNA expression of cytochrome p450 oxidoreductase (POR) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A total of 19 candidate single nucleotide polymorphisms (SNPs) located in the exons of POR were genotyped using Sanger sequencing from 476 HBV-related HCC patients who underwent hepatectomy between 2003 and 2013. The mRNA expression of POR in 212 patients with HBV-related HCC was obtained from GSE14520 dataset. Survival analysis was performed to investigate the association of POR variants and mRNA expression with overall survival (OS) and recurrence-free survival (RFS). Nomograms were used to predict the prognosis of HBV-related HCC patients. Gene set enrichment analysis (GSEA) was used to investigate the mechanism of POR in HBV-related HCC prognosis. The polymorphism POR-rs1057868 was significantly associated with HBV-related HCC OS (CT/TT vs. CC, hazard ratio [HR] = 0.69, 95% confidence interval [CI] = [0.54, 0.88], P = 0.003), but not significantly associated with RFS (CT/TT vs. CC, P = 0.378). POR mRNA expression was also significantly associated with HBV-related HCC OS (high vs. low, HR = 0.61, 95% CI = [0.38, 0.97], P= 0.036), but not significantly associated with the RFS (high vs. low, P = 0.201). Two nomograms were developed to predict the HBV-related HCC OS. Furthermore, GSEA suggests that multiple gene sets were significantly enriched in liver cancer survival and recurrence, as well as POR-related target therapy in the liver. In conclusion, our study suggests that POR-rs1057868 and mRNA expression may serve as a potential postoperative prognosis biomarker in HBV-related HCC.

Place, publisher, year, edition, pages
IVYSPRING INT PUBL , 2019. Vol. 10, no 6, p. 1453-1465
Keywords [en]
hepatocellular carcinoma, cytochrome p450 oxidoreductase, prognosis, hepatitis B virus, hepatectomy
National Category
Basic Medicine
Identifiers
URN: urn:nbn:se:kth:diva-246295DOI: 10.7150/jca.28919ISI: 000459711200013OAI: oai:DiVA.org:kth-246295DiVA, id: diva2:1298928
Note

QC 20190325

Available from: 2019-03-25 Created: 2019-03-25 Last updated: 2019-05-13Bibliographically approved

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Liu, Zhengtao

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