Cell-free DNA analysis by whole-exome sequencing for hepatocellular carcinoma: a pilot study in Thailand

Liquid biopsy for cell-free DNA (cfDNA) is a non-invasive technique to characterize the genetic profile of a tumor. Despite being a valuable tool, there is no mutational profile of cfDNA from hepatocellular carcinoma (HCC) in patients from Thailand, where HCC is prevalent. The present study aimed to demonstrate the utility of using whole-exome sequencing of cfDNA to define the somatic mutation profiles of HCC in Thai patients who underwent nonoperative therapies.

The level of cfDNA was higher in HCC patients than in chronic hepatitis patients. Single nucleotide variations were present in somatic genes in cfDNA, including in ZNF814, HRNR, ZNF492, ADAMTS12, FLG, OBSCN, TP53, and TTN. The co-occurrence of HRNR and TTN mutations in cfDNA was associated with shorter overall survival. These findings indicate that the mutational profiles of cfDNA reflected those of HCC tissue, and cfDNA could serve as a useful biomarker for diagnosis and prognosis in HCC patients.