Prognostic Role of Serum Cytokeratin-19 Fragment (CYFRA 21-1) in Patients with Hepatocellular Carcinoma

SIMPLE SUMMARY: The prognosis of hepatocellular carcinoma is mainly driven by the stage of the tumor and by the overall liver function status. However, survival rates of patients with hepatocellular carcinoma are heterogeneous. In this study, we investigated whether circulating biomarkers might allow us to stratify the survival of patients with a new diagnosis of hepatocellular carcinoma. We observed that three biomarkers (namely AFP, PIVKA-II, and CYFRA 21-1) were independent predictors of overall survival. In addition, the combined use of these biomarkers allowed us to further stratify patients with hepatocellular carcinoma, according to their survival probability. This approach might help clinicians to tailor more personalized treatment strategies. ABSTRACT: Keratin 19 (K19) is a cancer stem cell marker expressed by a subpopulation of hepatocellular carcinoma (HCC), associated with tumor aggressiveness. We evaluated the prognostic value of serum K19 fragment (CYFRA 21-1), in comparison or in combination with alpha-fetoprotein (AFP) and protein induced by vitamin-K absence or antagonist-II (PIVKA-II), in patients with HCC. A total of 160 patients (28F/132M; median age 62, range 44–86 years) with a new diagnosis of HCC and available serum samples collected at tumor diagnosis were analyzed retrospectively. Median overall survival (OS) after HCC diagnosis was 35.1, 95% CI 27.1–70.5 months. Multivariate Cox regression analysis showed that CYFRA 21-1 > 2.7 ng/mL (hazard ratio (HR) = 3.39, p < 0.001), AFP > 20 ng/mL (HR = 2.27, p = 0.007), and PIVKA-II > 200 mAU/mL (HR = 2.17, p = 0.020) were independent predictors of OS. The combination of biomarkers positivity allowed us to stratify patients with HCC into four risk categories associated with a progressively lower survival probability (log-rank test, p < 0.001). CYFRA 21-1 resulted an independent prognostic factor of patients with HCC and its combination with AFP and PIVKA-II might be useful to tailor personalized treatment strategies.