Liquid Biopsy in Hepatocellular Carcinoma: ctDNA as a Potential Biomarker for Diagnosis and Prognosis.
By John Joseph Pack MD
Published on 09/15/2025
Current Onological Reports. 2025 Jun;27(6):791-802. doi: 10.1007/s11912-025-01681-3. Epub 2025 May 9.
Liquid Biopsy in Hepatocellular Carcinoma: ctDNA as a Potential Biomarker for Diagnosis and Prognosis
William Yang 1, Romario Nguyen 1, Fatema Safri 1, Muhammad J A Shiddiky 2, Majid E Warkiani 3, Jacob George # 4 5, Liang Qiao # 6 7
Affiliations Expand
PMID: 40343687
PMCID: PMC12227495
DOI: 10.1007/s11912-025-01681-3
Abstract
Purpose of review: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with rising incidence and mortality. Early-stage HCC is often asymptomatic, and the lack of reliable early diagnostic markers leads to late-stage diagnosis with limited treatment options. Current treatment relies on tumour staging and patient status, but accurate staging requires invasive procedures that fail to capture tumour heterogeneity and progression. There is an urgent need for less invasive diagnostic strategies, such as liquid biopsy technologies, which allow for repeated sampling and real-time analysis of tumour dynamics. Liquid biopsies, including circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA), offer the potential to monitor recurrence, metastasis, and treatment responses, potentially transforming HCC clinical management by enabling earlier intervention and personalised treatment strategies.
Recent findings: Recent studies emphasise the potential of ctDNA as a non-invasive biomarker by targeting DNA methylation for early HCC detection, enabling timely intervention and personalised treatment to improve patient outcomes. Comparative analyses have shown that ctDNA mutation testing outperforms alpha-fetoprotein (AFP), with a sensitivity of 85% and a specificity of 92%, compared to 60% sensitivity and 80% specificity for AFP. Additionally, profiling the ctDNA mutation landscape of 100 HCC patients has identified recurrent mutations in genes such as TP53, CTNNB1, and AXIN1. ctDNA appears to be a promising non-invasive biomarker in the clinical management of HCC patients, with the sensitivity and specificity improving by 41.67% and 15% respectively. The ctDNA mutations, particularly those targeting DNA methylation, highlight great potential for precision medicine, critical for early diagnosis and prognosis of HCC.
Keywords: Cell-free DNA (cfDNA); Circulating tumour DNA (ctDNA); Circulating tumour cells (CTCs); Hepatocellular carcinoma (HCC).
© 2025. The Author(s).
Reviewer Comments: The above review details the fascinating and potentially limitless applications of what is now being called liquid biopsy. As this technology is developed, it is likely to have a major impact on how we detect, surveil, and treat patients with cancer. Liquid biopsy, which can detect circulating tumor cells and circulating tumor DNA, may become one of the most important advances in oncology of the 21st century. Its potential appears to be unlimited at this early stage. Reprinted verbatim as free public access article on Pub Med. John Joseph Pack MD, Internal Medicine
