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The prognostic value of differentially expressed CYP3A subfamily members for hepatocellular carcinoma

Authors Yu T, Wang X, Zhu G, Han C, Su H, Liao X, Yang C, Qin W, Huang K, Peng T

Received 9 December 2017

Accepted for publication 25 March 2018

Published 25 June 2018 Volume 2018:10 Pages 1713—1726

DOI https://doi.org/10.2147/CMAR.S159425

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Antonella D'Anneo


Tingdong Yu, Xiangkun Wang, Guangzhi Zhu, Chuangye Han, Hao Su, Xiwen Liao, Chengkun Yang, Wei Qin, Ketuan Huang, Tao Peng

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China

Objective: The activities of four cytochrome P3A (CYP3A) subfamily members (CYP3A4, CYP3A5, CYP3A7, and CYP3A43) are well documented in drug metabolism. However, the association between CYP3A subfamily members and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic value of CYP3A subfamily mRNA expression levels with HCC prognosis.
Materials and methods:
Data from a total of 360 HCC patients were retrieved from The Cancer Genome Atlas database, and data from 231 HCC patients were retrieved from the Gene Expression Omnibus database. Kaplan–Meier analysis and Cox regression models were utilized to determine median survival, overall survival, and recurrence-free survival. Hazard ratios and 95% CI were calculated.
Results:
Low expression of CYP3A4, CYP3A5, and CYP3A43 in the tumor tissue was associated with short median survival (crude p=0.004, 0.001, and 0.001; adjusted p=0.022, 0.005, and 0.013, respectively). Joint-effects combination analysis of CYP3A4, CYP3A5/CYP3A4, CYP3A43/CYP3A5, and CYP3A43 revealed that high expression groups of two genes (group C, group c, group 3) were associated with a reduced risk of death, as compared to low expression of two genes (group A, group a, group 1), and the adjusted p values were 0.001, 0.004, and 0.001, respectively. Joint-effects analysis of CYP3A4, CYP3A5, and CYP3A43 showed that groups III and IV had a reduced risk of death, as compared to group I (adjusted p=0.024 and 0.002, respectively).
Conclusion:
CYP3A4, CYP3A5, and CYP3A43 mRNA expression levels are potential prognostic markers of HCC.

Keywords: mRNA expression, CYP3A subfamily, hepatocellular carcinoma, prognosis, biomarker

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