J Cancer 2019; 10(6):1453-1465. doi:10.7150/jca.28919 This issue Cite
Research Paper
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.
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