Des-Gamma-Carboxy Prothrombin Is Associated With Tumor Aggressiveness and Recurrence in Resected Early-Stage Hepatocellular Carcinoma: A Clinicopathological and Molecular Analysis.

Abstract

Aim: Alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) are widely used tumor markers for hepatocellular carcinoma (HCC); however, their relative prognostic significance in early-stage disease remains unclear. This study aimed to compare the prognostic impact of AFP and DCP in resected HCC and to explore their underlying molecular characteristics.

Methods: We retrospectively analyzed 482 patients who underwent curative resection for HCC. Patients were classified into four groups according to AFP and DCP levels: Negative, AFP-only, DCP-only, and Dual-positive. Recurrence-free survival (RFS) and prognostic factors were evaluated. In a subset of 204 patients, gene expression profiling was conducted to investigate molecular differences.

Results: Among BCLC stage 0/A patients (n = 406), RFS was stratified according to tumor marker status. The DCP-only group showed significantly worse RFS than the AFP-only group (5-year RFS: 39.5% vs. 52.7%, p = 0.026) and was characterized by larger tumor size (median, 39 vs. 18 mm, p < 0.001) and more frequent portal venous invasion (29% vs. 14%, p = 0.052). Multivariable analysis identified elevated DCP as an independent prognostic factor (hazard ratio 1.48, p = 0.004). In contrast, among stage B/C patients (n = 76), survival outcomes were uniformly poor and not stratified by tumor marker. Gene expression analysis revealed the upregulation of SFN and downregulation of DCN in DCP-elevated tumors, suggesting extracellular matrix destabilization that may contribute to tumor aggressiveness.

Conclusions: Elevated DCP reflects aggressive tumor biology and identifies patients at high risk of recurrence after resection for BCLC stage 0/A HCC. These findings support the clinical utility of DCP for risk stratification and postoperative surveillance for early-stage HCC.