Characteristics of Recurrent Hepatocellular Carcinoma Based on Serum AFP, PIVKA-II, and Genetic Mutations

Background and Objectives: Reliable tools for evaluating tumor biology and forecasting clinical outcomes in recurrent hepatocellular carcinoma (HCC) remain scarce, and molecular characterization through genetic profiling is equally limited in this setting. This investigation explores whether serum tumor marker expression patterns correlate with genomic mutation profiles, and whether such correlations may facilitate more accurate prediction of tumor biology and patient prognosis in recurrent HCC. Materials and Methods: We analyzed a cohort of 20 patients who underwent curative-intent resection for both primary and recurrent HCC. Tumor specimens collected at the time of each operation were subjected to targeted next-generation sequencing for mutation profiling. Based on pre-operative serum levels of AFP (alpha-fetoprotein) and PIVKA-II (Protein Induced by Vitamin K Absence or Antagonist-II) measured before each surgery, patients were stratified into four biomarker subgroups. Those who maintained the same biomarker subgroup at both operations were designated the 'serum concordant group', whereas those who transitioned between subgroups were classified as the 'serum discordant group'. Clinical characteristics and mutation data were subsequently compared between these two classifications. Results: The interval from primary surgery to disease recurrence was significantly shorter in the serum concordant group relative to the serum discordant group (mean 11.16 ± 1.86 vs. 44.8 ± 9.45 months, p < 0.001). Additionally, disease-free survival following reoperation was significantly inferior in the concordant group compared with the discordant group (p = 0.039). Regarding mutational patterns, the concordant group demonstrated shared gene mutations between primary and recurrent lesions, while the discordant group exhibited divergent mutational landscapes across both timepoints. Conclusions: The concordance or discordance of serum tumor marker profiles between primary and recurrent HCC lesions may serve as a clinically accessible surrogate for underlying tumor biology and prognostic stratification. These results are preliminary and hypothesis-generating. Further studies in larger, independent cohorts are warranted to confirm the observed associations.