Genetic Variants in the EPCAM Gene Is Associated with the Prognosis of Transarterial Chemoembolization Treated Hepatocellular Carcinoma with Portal Vein Tumor Thrombus

Xiaohe Yu,Xu Guo,Xiaojun Huang,Naijian Ge,Yefa Yang,Qichao Huang,Shaogui Wan,Shuqun Shen,Jingliang Xing,Jun Liang,Ferruccio Bonino

doi:10.1371/journal.pone.0093416

Abstract

The epithelial cell adhesion molecule (EPCAM) is involved in the tumorigenesis and progression of many malignancies, including hepatocellular carcinoma (HCC). Single nucleotide polymorphisms (SNPs) of EPCAM have been reported to be with the risk and prognosis of several malignancies. However, the association of SNPs in EPCAM gene with the prognosis of HCC patients has never been investigated. In this study, two functional SNPs (rs1126497 and rs1421) in the EPCAM gene were selected and genotyped in a cohort of 448 unresectable Chinese HCC patients treated by TACE. The association of the two SNPs with the overall survival (OS) of patients was assessed by univariate and multivariate Cox proportional hazards model and Kaplan-Meier curve. Our data showed that there was no significant association between either SNP and OS of patients. However, in the stratified analysis, the variant-containing genotypes (WV+VV) of SNP rs1126497 exhibited a significant association with poorer OS in HCC patients who had portal vein tumor thrombus (PVTT) in multivariate analysis of Cox proportional hazard model (hazard ratio, 1.71; 95% confidence interval, 1.16–2.53, P = 0.007), and in Kaplan-Meier curve analysis (P = 0.023), comparing to those carrying wild-type genotype. Our results suggest that SNP rs1126497 in the EPCAM gene may serve as an independent prognosis biomarker for unresectable HCC patient with PVTT, which warranted further validating investigation.

Highlights

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide, and its morbidity and mortality rates have escalated in recent years[1]
We examined the genotype in two functional SNP loci in epithelial cell adhesion molecule (EPCAM) gene and assessed the associations of the two SNPs with the overall survival (OS) in a Chinese cohort of 448 unresectable HCC patients treated by Transarterial chemoembolization (TACE)
We assessed the effects of 2 functional SNPs in the EPCAM gene on the OS of a cohort of unresectable Chinese HCC patients treated by TACE

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide, and its morbidity and mortality rates have escalated in recent years[1]. Despite improvements in surveillance and clinical treatment strategies, the prognosis of HCC patients remains poor. Cohort studies with long-term follow-ups have showed a median survival time of 20 months for patients with HCC at intermediate stages and 12 months for patients at advanced stages with portal vein invasion[5]. Traditional clinicopathological parameters such as tumor morphology, histopathological features, concentration of serum alpha fetoprotein (AFP) and tumor stage offer limited information for prognosis prediction and fail to guide the therapeutic schedule for individual patient. It is extremely urgent to explore novel biomarkers to discriminate patient groups with different clinical outcomes and direct the treatment for HCC patients

Methods

Results

Conclusion