rs62139665 Polymorphism in the Promoter Region of EpCAM Is Associated With Hepatitis C Virus-Related Hepatocellular Carcinoma Risk in Egyptians

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.

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Clinical significance of SNP (rs2596542) in histocompatibility complex class I-related gene A promoter region among hepatitis C virus related hepatocellular carcinoma cases

Journal of Advanced Research ◽

10.1016/j.jare.2017.03.004 ◽

2017 ◽

Vol 8 (4) ◽

pp. 343-349 ◽

Cited By ~ 7

Author(s):

Amal A. Mohamed ◽

Ola M. Elsaid ◽

Eman A. Amer ◽

Heba H. Elosaily ◽

Mohamed I. Sleem ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Clinical Significance ◽

Promoter Region ◽

Class I ◽

Complex Class ◽

Related Gene ◽

Histocompatibility Complex

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Characterization of liver histopathology in a transgenic mouse model expressing genotype 1a hepatitis C virus core and envelope proteins 1 and 2

Journal of General Virology ◽

10.1099/vir.0.80969-0 ◽

2005 ◽

Vol 86 (8) ◽

pp. 2185-2196 ◽

Cited By ~ 49

Author(s):

Turaya Naas ◽

Masoud Ghorbani ◽

Ikuri Alvarez-Maya ◽

Michael Lapner ◽

Rashmi Kothary ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Mouse Model ◽

Protein Expression ◽

Transgenic Mouse ◽

Transgenic Mouse Model ◽

Structural Proteins ◽

Hcv Rna ◽

Hcv Structural Proteins

Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatocellular carcinoma worldwide. The purpose of this study was to determine how the HCV structural proteins affect the dynamic structural and functional properties of hepatocytes and measure the extra-hepatic manifestations induced by these viral proteins. A transgenic mouse model was established by expressing core, E1 and E2 proteins downstream of a CMV promoter. HCV RNA was detected using RT-PCR in transgenic mouse model tissues, such as liver, kidney, spleen and heart. Expression of the transgene was analysed by real-time PCR to quantify viral RNA in different tissues at different ages. Immunofluorescence analysis revealed the expression of core, E1 and E2 proteins predominantly in hepatocytes. Lower levels of protein expression were detected in spleen and kidneys. HCV RNA and viral protein expression increased in the liver with age. Histological analysis of liver cells demonstrated steatosis in transgenic mice older than 3 months, which was more progressed with age. Electron microscopy analysis revealed alterations in nuclei, mitochondria and endoplasmic reticulum. HCV structural proteins induce a severe hepatopathy in the transgenic mouse model. These mice became more prone to liver and lymphoid tumour development and hepatocellular carcinoma. In this model, the extra-hepatic effects of HCV, which included swelling of renal tubular cells, were mild. It is likely that the HCV structural proteins mediate some of the histological alterations in hepatocytes by interfering with lipid transport and liver metabolism.

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Diagnostic Accuracy of Circulating microRNAs for Hepatitis C Virus-Associated Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

10.21203/rs.3.rs-251826/v1 ◽

2021 ◽

Author(s):

Jiajie Zhang ◽

Jiepeng Tong ◽

Yicheng Huang ◽

Li Zhang ◽

Wei Yu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Diagnostic Accuracy ◽

Meta Analysis ◽

Cochrane Library ◽

Circulating Mirnas ◽

Likelihood Ratios ◽

Circulating Micrornas ◽

Mirna Clusters

Abstract Aims: The purpose of this study was to perform an assessment of circulating microRNAs as promising biomarker for Hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCV-HCC) through a meta-analysis.Methods: A comprehensive literatures search extended up to March 1, 2020 in PubMed, Cochrane library, Embase, Web of Science, Scopus and Ovid databases. The collected data were analyzed by random-effects model because of high heterogeneity, the pooled sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were used to explore the diagnostic performance of circulating miRNAs. Subgroup and threshold effect analysis were further carried out to explore the heterogeneity. Results: Overall, 16 articles that included a total of 3606 HCV-HCC patients and 3387 HCV patients without HCC were collected. The pooled estimates indicated miRNAs could distinguish HCC patients from chronic hepatitis C (CHC) and HCV-associated liver cirrhosis (HCV-LC), with a SEN of 0.83 (95% CI, 0.79-0.87), a SPE of 0.77 (95% CI, 0.71-0.82), a DOR of 17 (95% CI, 12-28), and an AUC of 0.87 (95% CI, 0.84-0.90). The combination of miRNAs and AFP showed a better diagnostic accuracy than each alone. Subgroup analysis demonstrated that diagnostic accuracy of miRNAs was better for plasma types, up-regulated miRNAs, and miRNA clusters. There was no evidence of publication bias in Deeks’ funnel plot.Conclusions: The summarized results suggested that circulating miRNAs, especially for miRNA clusters, have a relatively high diagnostic value for HCV-HCC, which could be served as non-invasive screening tool.

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