CTNNB1 Polymorphism (rs121913407) in Circulating Tumor DNA (ctDNA) in Egyptian Hepatocellular Carcinoma Patients: A Case-Control Study

Abstract

Hepatocellular carcinoma is a primary tumor of the liver that arises from hepatocytes. It constitutes about 90% of primary liver tumors. HCC is the sixth most common cancer globally and the fourth in Egypt. It develops on top of chronic liver disease especially among patients with chronic hepatitis B and C. Many risk factors contribute to development of HCC, however, cirrhosis is considered the most important risk factor linked to development of HCC. Despite the importance of tissue biopsy in confirming the diagnosis of HCC, it is an invasive procedure. Meanwhile, liquid biopsy has emerged as a promising alternative for tissue biopsy for early detection of HCC. Circulating tumor DNA, which is part of cfDNA, is double-stranded DNA fragments around 160 base pair having the same molecular characteristics of the tumor it originates from. The present study investigated the clinical utility of peripheral blood ctDNA to assess the presence of CTNNB1 rs121913407 (C.133T>C) polymorphism in HCC patients (EHCC and AHCC) in comparison with the findings in HCV patients and healthy controls to determine its role in hepatocarcinogenesis. For this purpose, samples were collected from twenty-eight (28) HCC patients. The patients' group were further subclassified according to BCLC classification into EHCC and AHCC patients. In addition, we included ten (10) patients diagnosed as HCV positive patients as pathological controls and ten (10) healthy individuals as healthy controls. The study revealed a highly significant difference among all the studied groups regarding INR, serum AST, ALT, total bilirubin and BUN levels, Moreover, multivariant regression analysis showed that the most sensitive variables that can predict HCC were serum albumin and INR. All of our studied cases (EHCC and AHCC) in addition to HCV and healthy control groups were CTNNB1 wild (TT) genotype. In conclusion, none of our recruited subjects showed CTNNB1 rs121913407 single nucleotide polymorphism in Egyptian HCC patients. One reason for our observed negative results could be attributed to the small number of cases in our study. Moreover, these speculations should be supported by sequencing either ctDNA from blood samples or DNA from tissue samples from t