Liquid Biopsy-Based Profiling of TP53 Gene Hotspot Mutations in HBV-Induced Chronic Liver Disease and Hepatocellular Carcinoma Patients: A Study From Bangladesh.

BACKGROUND

The tumor protein (TP53) gene is a common driver gene for somatic mutations in hepatocellular carcinoma(HCC), and detection may provide insight into evaluating disease progression. Circulating cell-free DNA (cfDNA) from liquid biopsy has emerged as a promising noninvasive biopsy material for identifying potential genetic alterations. This study explored the mutational signature of the TP53 gene in Hepatitis B virus (HBV)-infected chronic liver disease (CLD) and HCC patients from cfDNA.

METHOD: A total of 80 participants: 30 HCC, 30 CLD, and 20 healthy controls were included in this cross-sectional study. cfDNA was extracted from aseptically collected peripheral venous blood. TP53 (R249S) gene was amplified using selected primers via conventional PCR and visualized on a 2% agarose gel electrophoresis. Amplified products underwent Sanger sequencing; mutational analysis was done using MEGA11 software compared with the reference sequence.

RESULT: TP53 hotspot mutations were found in 23.3% (7/30) of HCC patients. Mutational frequencies were detected: 13.3% (4/30) at position 746G > A (R249S), 6.7% (2/30) at 747G > A (R249S), and 3.3% (1/30) at 735C > T (G245S). Among CLD patients, a single hotspot mutation (3.3%) was detected at position 744G > A/T(R248Q/W). However, no hotspot mutation was detected in healthy controls. All HCC patients with mutations (7/7, 100%) had elevated ALT, AST, serum bilirubin, and AFP levels, and in the unmutated (wild) group, these were 69.6%, 47.8%, 30.4%, and 60.9%, respectively. The mean AST and AFP levels were significantly higher in mutated patients compared with the wild group.

CONCLUSION

Detection of TP53 gene mutations along with biochemical markers in the management of HCC is evident, and it may play an important role in targeted therapy and personalized treatment plans.