Correlation Analysis Between Circulating Tumor DNA and Prognosis in Patients with Hepatocellular Carcinoma

Circulating tumor DNA (ctDNA) is a noninvasive biomarker for tumor burden. Blood-based assays utilizing ctDNA copy number aberrations and fragment size show promise in hepatocellular carcinoma (HCC), but their prognostic value is unclear. This study evaluated the clinical relevance of a ctDNA-based score in predicting HCC prognosis.

Clinical and ctDNA data from 93 HCC patients were analyzed. Patients were stratified by a predefined ctDNA score cutoff. Group comparisons used chi-square tests. Kaplan-Meier and multivariate Cox regression analyses assessed prognostic relevance.

Elevated ctDNA scores were associated with aggressive features: higher AFP and PIVKA-II levels, larger tumor size, macrovascular invasion, and advanced TNM stage (all P < 0.001). Patients with ctDNA scores > 0.61199 had significantly worse overall survival (OS). Univariate analysis identified 19 OS-associated variables, including inflammatory markers, biochemical indices, and tumor burden parameters. Multivariate analysis confirmed ctDNA score > 0.61199 (HR = 6.99, 95% CI 2.34-20.85, P < 0.001), AFP > 400 ng/mL (HR = 0.28, 95% CI 0.13-0.61, P = 0.001), ALB < 35.6 g/L (HR = 3.29, 95% CI 1.34-8.06, P = 0.009), and tumor number > 3 (HR = 3.85, 95% CI 1.58-9.40, P = 0.003) as independent prognostic determinants.

Elevated ctDNA scores are strongly associated with adverse outcomes in HCC, highlighting their potential as a noninvasive prognostic biomarker. Integrating ctDNA assessment could improve risk stratification and treatment decisions, warranting validation in prospective studies.