Abstract
Hepatocellular carcinoma (HCC) is a universal health problem that is particularly alarming in Egypt. The major risk factor for HCC is hepatitis C virus (HCV) infection which is a main burden in Egypt. The epithelial cell adhesion molecule (EpCAM) is a stem cell marker involved in the tumorigenesis and progression of many malignancies, including HCC. We investigated the association of -935 C/G single nucleotide polymorphism in EpCAM promoter region (rs62139665) with HCC risk, EpCAM expression and overall survival in Egyptians. A total of 266 patients (128 HCV and 138 HCC cases) and 117 age- and sex-matched controls participated in this study. Genotyping, performed using allelic discrimination and confirmed by sequencing, revealed a significant association between EpCAM rs62139665 and HCC susceptibility, with higher GG genotype and G allele distribution in HCC patients than in non-HCC subjects. Such association was not detected in HCV patients compared to controls. EpCAM gene expression levels, determined in blood by RT-qPCR, and its serum protein expression levels, determined by ELISA, were significantly higher in GG relative to GC+CC genotype carriers in HCV and HCC patients in a recessive model. ROC analysis of EpCAM protein levels revealed significant discriminatory power between HCC patients and non-HCC subjects, with improved diagnostic accuracy when combining α-fetoprotein and EpCAM compared to that of α-fetoprotein alone. Altogether, EpCAM rs62139665 polymorphism is significantly associated with HCC and with EpCAM gene and protein expression levels in the Egyptian population. Moreover, serum EpCAM levels may hold promise for HCC diagnosis and for improving the diagnostic accuracy of α-fetoprotein.
Highlights
Hepatitis C virus (HCV) infection is a major burden in Egypt, infecting almost 14.7% of the population
The GG genotype and G allele frequencies were significantly higher in the Hepatocellular carcinoma (HCC) group compared to the hepatitis C virus (HCV) patients (P = 0.0005 and P < 0.0001, respectively) and to the control subjects (P = 0.04 and P = 0.001, respectively), while no significant difference was found between HCV and control groups
Egypt endures the highest incidence of HCV infection that is considered a main predisposing factor for the progression of HCC
Summary
Hepatitis C virus (HCV) infection is a major burden in Egypt, infecting almost 14.7% of the population. Chronic HCV is the leading cause of liver-related death in Egypt [1]. Hepatocellular carcinoma (HCC) is considered the third cause of cancer-related mortality globally [2]. This high mortality rate could be attributed to the late manifestation of HCC symptoms and, its late diagnosis. Such diagnostic inadequacy is prominent in lower resource settings with limited screening tools [3]. The presence of cirrhosis increases the risk for HCC, some patients develop HCC in non-cirrhotic livers and in the absence of inflammation [5]. Several studies reported some genetic and epigenetic defects that lead to the onset of HCC [6, 7]
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