Clinical Utility of CTNNB1 (c.121A>G) Mutation in Circulating Tumor DNA in Egyptian Patients with Hepatocellular Carcinoma: A Case-Control Study

Abstract

SUMMARY epatocellular carcinoma (HCC) is a primary tumor of the liver. It constitutes about 90% of all primary liver cancers and usually develops in the setting of chronic liver disease. In Egypt, HCC causes a significant public health problem with a rising incidence due to the strong link between HCC and the high prevalence of viral hepatitis and its complications mainly hepatitis C virus (HCV). CTNNB1 mutations are among the most frequent genetic alterations in HCC and have been reported in 20~40% of cases. CTNNB1 mutations are more common in HCV-related HCCs compared to HBV-related HCCs, Mutations can result in sustained aberrant activation of the Wnt/β-catenin pathway and thus dysregulate multiple cellular functions, including proliferation, apoptosis, and cell motility. This case control study aimed to investigate the clinical utility of CTNNB1 (rs121913412) (c.121A>G) mutation (SNP) in peripheral blood ctDNA in patients with early and late stage HCC in comparison to (Chronic Hepatitis C virus patients) and healthy controls. Patients presented to HCC clinic in Tropical medicine department, Ain shams center for organ transplantation (ASCOT) and clinical patology department, Ain shams university hospitals were enrolled in the study from October 2020 through April 2021. The included patients were adult patients with confirmed HCC of both genders. All patients underwent full medical history, clinical examination, full labs and genotyping for CTNNB1, and CT triphasic only for HCC patients. The included patients were 30 patients with HCC. The mean age of the patients was with mean (SD 58.92 ± 8. 47) with male predominance, males were 84% in the studied population. The most common radiological characteristic of HCC group was single HFL in 50% of the patients. This study revealed that the most common complication was ascites 63.3% and PVT 40%. The important lab investigations of the study group (No= 50 ) the mean AST was 59 mg/dl, mean ALT was 53.6 mg/dl. mean T.bil was 1 mg/dl, mean Alb was 3.4 mg/dl, mean INR was 1.2 mg/dl, mean Bun was 23.9 mg/dl, mean creat was 1.1 mg/dl and Mean alphafeto protein in HCC patients was 5345 ± 18347 mg/dl. The 30 cases of HCC divided in 14 early, 16 late and 16 case from the whole cases fulfilled the Milan criteria. Most of HCC pts were child B (43.3%), 10 pts (33.3%) were child A and 7 pts (23.3%) were child c. For the BCLC staging system, 8 pts (26.7%) were stage A (early stage) and 7 pts (23.3%) were stage D. Three cases from 50 cases had CTNNB1 gene mutation, CTNNB1 gene mutation appeared only in HCC cases while healthy and HCV +ve controls had no mutation. The CTNNB1 gene mutation in HCC cases appeared in 3 pts fulfilled the milan criteria but don’t fullfill UCSF criteria.