The prognostic value of CYP2C subfamily genes in hepatocellular carcinoma.

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

doi:10.1002/cam4.1299

Abstract

Cytochrome P2C (CYP2C) subfamily members (CYP2C8,CYP2C9,CYP2C18, and CYP2C19) are known to participate in clinical drug metabolism. However, the association between CYP2C subfamily members and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic value of CYP2C subfamily gene expression levels with HCC prognosis. Data of 360 HCC patients in The Cancer Genome Atlas database and 231 in the Gene Expression Omnibus database were analyzed. Kaplan–Meier analysis and a Cox regression model were used to ascertain overall survival and recurrence‐free survival, and to calculate median survival time using hazard ratios (HR) and 95% confidence intervals (CI). In TCGA database, low expression of CYP2C8,CYP2C9, and CYP2C19 in tumor tissue was associated with a short median survival time (all crude P = 0.001, adjusted P = 0.004, P = 0.047, and P = 0.020, respectively). In TCGA database, joint effects analysis of the combinations of CYP2C8 and CYP2C9,CYP2C8 and CYP2C19, and CYP2C9 and CYP2C19 revealed that high expression of two genes (group 4; group IV, group d) was associated with a reduced risk of death as compared to low expression (group 1, group I, and group a) (adjusted P = 0.005, P = 0.013, and P = 0.016, respectively). In TCGA database, joint effects analysis of CYP2C8,CYP2C9, and CYP2C19 showed that the risk of death from HCC was lower for groups C and D than for group A (adjusted P = 0.012 and P = 0.008, respectively). CYP2C8,CYP2C9, and CYP2C19 gene expression levels are potential prognostic markers of HCC following hepatectomy.

Highlights

Liver cancer is the fifth most commonly diagnosed cancer and the second most frequent cause of cancer-related deaths in men and the seventh most frequently diagnosed cancer and the sixth leading cause of cancer-related deaths in women worldwide [1]
TNM stage was significantly associated with median survival time (MST) (P < 0.001), but not sex, age, body mass index (BMI), or race
Nodal status, primary tumor size, Barcelona Clinic Liver Cancer (BCLC) stage, cirrhosis status, and AFP level were related to overall survival (OS), while sex, cirrhosis status, primary tumor size, and BCLC stage were related to recurrence- free survival (RFS) (P = 0.001, 0.019, 0.020, and

Summary

Introduction

Liver cancer is the fifth most commonly diagnosed cancer and the second most frequent cause of cancer-related deaths in men and the seventh most frequently diagnosed cancer and the sixth leading cause of cancer-related deaths in women worldwide [1]. Hepatocellular carcinoma (HCC), the major histological type, accounts for most (70–85%) cases of primary liver cancer worldwide [3]. Role of CYP2C in Hepatocellular Carcinoma exposure, obesity, diabetes, nonalcoholic steatohepatitis, alcohol ingestion, hemochromatosis, and other metabolic diseases are the primary risk factors for HCC [4]. Despite advances in several treatment strategies, such as liver resection, liver transplantation, percutaneous ethanol injection, transcatheter arterial chemoembolization, transarterial radiation, microwave ablation, and systemic therapy, the prognosis of HCC remains unsatisfactory because of late- stage diagnosis [5], which has resulted in a reported 5-year survival rate of only 7% [6]. The identification of molecular biomarkers for the early diagnosis of HCC is crucial to provide more effective therapies and improve patient prognosis

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