J Cancer 2019; 10(6):1453-1465. doi:10.7150/jca.28919

Research Paper

Genetic variants and Expression of Cytochrome p450 Oxidoreductase Predict Postoperative Survival in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma

Ketuan Huang1*, Xiwen Liao1*, Chuangye Han1, Xiangkun Wang1, Tingdong Yu1, Chengkun Yang1, Xiaoguang Liu1,2, Long Yu1,3, Zhiwei Chen1, Wei Qin1, Guangzhi Zhu1, Hao Su1, Zhengqian Liu1, Xianmin Zeng1, Xin Zhou1, Sicong Lu1, Jianlv Huang1,4, Yu Liang1, Zhengtao Liu1,5,6, Jianlong Deng1,7, 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, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong Province, People's Republic of China;
3. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan Province, People's Republic of China;
4. Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Guangxi Medical University, Nanning, 530031, Guangxi Zhuang Autonomous Region, People's Republic of China;
5. 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;
6. Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, SE-171 21, Sweden;
7. Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital of Guangxi Medical University, Yulin, 537000, Guangxi Zhuang Autonomous Region, People's Republic of China.
*These authors contributed equally to this work.

Abstract

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.

Keywords: hepatocellular carcinoma, cytochrome p450 oxidoreductase, prognosis, hepatitis B virus, hepatectomy

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How to cite this article:
Huang K, Liao X, Han C, Wang X, Yu T, Yang C, Liu X, Yu L, Chen Z, Qin W, Zhu G, Su H, Liu Z, Zeng X, Zhou X, Lu S, Huang J, Liang Y, Liu Z, Deng J, Ye X, Peng T. Genetic variants and Expression of Cytochrome p450 Oxidoreductase Predict Postoperative Survival in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma. J Cancer 2019; 10(6):1453-1465. doi:10.7150/jca.28919. Available from http://www.jcancer.org/v10p1453.htm