The prognostic value of postoperative circulating cell-free DNA in operable hepatocellular carcinoma

Abstract

Background: Tumor biomarkers are eagerly needed in monitoring the recurrence of operable hepatocellular carcinoma (HCC). Circulating cell-free DNA (cfDNA) is a promising noninvasive molecular biomarker for HCC. The current study aimed to evaluate the clinical significance of the postoperative cfDNA in operable HCC. Methods: This study enrolled 82 HCC patients from January 2018 to June 2019. All patients underwent liver surgery and were pathologically diagnosed with HCC. Postoperative blood samples were collected from each patient. A fluorometric dsDNA assay was used to measure the concentration of cfDNA. We explore the correlation between cfDNA and recurrence. Kaplan-Meier's curves were used to evaluate the recurrence-free survival (RFS). Univariate and multivariate Cox regression analyses were used for assessing the relative clinical variables in predicting recurrence. Results: Of the 82 HCC patients, 72 (87%) patients are male and the average age was 52.7 ± 12.8 years. The cfDNA-low and cfDNA-high groups had median recurrence times of 19.5 months and 14.0 months, respectively (p ¼ .023). Multivariate analysis showed that postoperative cfDNA, tumour number and microvascular invasion (p < .050) were independent risk factors for recurrence in operable HCC. Conclusions: Postoperative cfDNA is still a promising marker to predict prognosis in postoperative HCC patients although prospective and large multicenter clinical study is needed to further validate the relationship between cfDNA and HCC recurrence.

Cell-Free DNA Analysis by Whole-Exome Sequencing for Hepatocellular Carcinoma: A Pilot Study in Thailand

“…An increase in cfDNA in the blood circulation was observed primarily in patients with tumoral mass compared with non-tumor patients [ 27 ]. In concordance with previous studies in HCC [ 28 , 29 ], the levels of cfDNA were significantly higher in patients with HCC than in patients with CH and were associated with worse clinical parameters, including tumor size and BCLC stage. Specifically, the high levels of cfDNA were found in patients with advanced-stage HCC (BCLC stage C) compared with early-stage (stage A) and intermediate stage (stage B).…”

Identification and monitoring of mutations in circulating cell-free tumor DNA in hepatocellular carcinoma treated with lenvatinib

“…We previously reported that detection of ctDNA before surgery could predict microscopic vascular invasion of the portal vein and recurrence, especially extrahepatic metastasis within 2 years in HCC patients who underwent liver resection [ 18 ]. Several other studies have also examined the role of ctDNA as a predictive or prognostic marker [ 40 – 44 ]. For molecular-targeted therapies, some reports have shown that ctDNA is useful for evaluation of treatment response and resistance, such as RAS mutation in colorectal cancer or EGFR mutations in lung cancer, known as targeting driver genes [ 45 – 48 ].…”

Utility of Cell-Free DNA Detection in Transplant Oncology

“…Examples of cfDNA biomarkers that have been examined include cfDNA concentration, copy number aberrations (CNA), methylation density, TP53 hotspot mutations, methylation of RASSF1A, and GSTP1 genes [112][113][114][115]. Long and colleagues investigated the diagnostic value of ctDNA concentration as a marker for transplant rejection in patients with HCC post-liver transplant [115]. In this retrospective study, post-operative cfDNA were measured and evaluated as a biomarker for HCC recurrence.…”

“…There are limited studies that have evaluated the use of ctDNA to detect rejection post-liver transplantation indicated for HCC treatment. Specifically, studies that have evaluated the use of ctDNA detection for transplant rejection have been for other clinical indications, such as propionic acidemia, sepsis, cirrhosis, hemochromatosis, bile duct necrosis, sclerosing cholangitis, and inborn errors of metabolism [115,[117][118][119][120][121][122][123]. One of the first studies that investigated the presence of donor-specific DNA as a marker for graft rejection was from Lo and colleagues in 1998 [124].…”