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细胞色素P450氧化还原酶的基因变异与表达可预测乙型肝炎病毒相关肝细胞癌患者的术后生存率。

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

作者信息

Huang Ketuan, Liao Xiwen, Han Chuangye, Wang Xiangkun, Yu Tingdong, Yang Chengkun, Liu Xiaoguang, Yu Long, Chen Zhiwei, Qin Wei, Zhu Guangzhi, Su Hao, Liu Zhengqian, Zeng Xianmin, Zhou Xin, Lu Sicong, Huang Jianlv, Liang Yu, Liu Zhengtao, Deng Jianlong, Ye Xinping, Peng Tao

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.

Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong Province, People's Republic of China.

出版信息

J Cancer. 2019 Feb 23;10(6):1453-1465. doi: 10.7150/jca.28919. eCollection 2019.

Abstract

Our current study investigates the prognostic values of genetic variants and mRNA expression of cytochrome p450 oxidoreductase () in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A total of 19 candidate single nucleotide polymorphisms (SNPs) located in the exons of were genotyped using Sanger sequencing from 476 HBV-related HCC patients who underwent hepatectomy between 2003 and 2013. The mRNA expression of in 212 patients with HBV-related HCC was obtained from GSE14520 dataset. Survival analysis was performed to investigate the association of 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 in HBV-related HCC prognosis. The polymorphism -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], = 0.003), but not significantly associated with RFS (CT/TT vs. CC, = 0.378). mRNA expression was also significantly associated with HBV-related HCC OS (high vs. low, HR = 0.61, 95% CI = [0.38, 0.97], = 0.036), but not significantly associated with the RFS (high vs. low, = 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 -related target therapy in the liver. In conclusion, our study suggests that -rs1057868 and mRNA expression may serve as a potential postoperative prognosis biomarker in HBV-related HCC.

摘要

我们目前的研究调查了细胞色素P450氧化还原酶(POR)的基因变异和mRNA表达在乙型肝炎病毒(HBV)相关肝细胞癌(HCC)中的预后价值。使用桑格测序法对2003年至2013年间接受肝切除术的476例HBV相关HCC患者中位于POR外显子的总共19个候选单核苷酸多态性(SNP)进行基因分型。从GSE14520数据集中获得212例HBV相关HCC患者的POR mRNA表达。进行生存分析以研究POR变异和mRNA表达与总生存期(OS)和无复发生存期(RFS)的关联。使用列线图预测HBV相关HCC患者的预后。基因集富集分析(GSEA)用于研究POR在HBV相关HCC预后中的机制。多态性位点-rs1057868与HBV相关HCC的OS显著相关(CT/TT与CC相比,风险比[HR]=0.69,95%置信区间[CI]=[0.54,0.88],P=0.003),但与RFS无显著关联(CT/TT与CC相比,P=0.378)。POR mRNA表达也与HBV相关HCC的OS显著相关(高表达与低表达相比,HR=0.61,95%CI=[0.38,0.97],P=0.036),但与RFS无显著关联(高表达与低表达相比,P=0.201)。开发了两个列线图来预测HBV相关HCC的OS。此外,GSEA表明多个基因集在肝癌生存和复发以及肝脏相关靶向治疗中显著富集。总之,我们的研究表明,-rs1057868和POR mRNA表达可能作为HBV相关HCC潜在的术后预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ded/6485213/27d7ada00496/jcav10p1453g001.jpg

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