Des‐Gamma‐Carboxy Prothrombin Is Associated With Tumor Aggressiveness and Recurrence in Resected Early‐Stage Hepatocellular Carcinoma: A Clinicopathological and Molecular Analysis
Katsuhisa Ohgi, Keiichi Ohshima, Michiie Sakamoto, Yae Kanai, Takeshi Nagashima, Ryo Ashida, Shimpei Otsuka, Hideyuki Dei, Satoshi Matsui, Keiichi Hatakeyama, Kenichi Urakami, Yasuto Akiyama, Katsuhiko Uesaka, Teiichi Sugiura, Ken YamaguchiABSTRACT
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.