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. 2020 Sep 28;12(10):2776.
doi: 10.3390/cancers12102776.

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

Gian Paolo Caviglia  1 , Michela Ciruolo  2 , Antonella Olivero  1 , Patrizia Carucci  2 , Emanuela Rolle  2 , Chiara Rosso  1 , Maria Lorena Abate  1 , Alessandra Risso  2 , Davide Giuseppe Ribaldone  1   2 , Francesco Tandoi  3 , Giorgio Maria Saracco  1   2 , Elisabetta Bugianesi  1   2 , Silvia Gaia  2
Affiliations

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

Gian Paolo Caviglia et al. Cancers (Basel). .

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.

Keywords: AFP; BCLC; HCC; PIVKA-II; biomarker; prognosis.

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Conflict of interest statement

G.P.C. received research grants from Fujirebio Europe and Fujirebio Diagnostics AB. All other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
CYFRA 21-1 (A), AFP (B), and PIVKA-II (C) serum levels among the different BCLC stages. Due to the low number of patients with end-stage HCC (n = 3), patients with BCLC stage C and D were merged. Hollow circles indicate values that are larger than the upper quartile plus 1.5 times the interquartile range while red squares indicate values that are larger than the upper quartile plus 3 times the interquartile range. Abbreviations—alpha-fetoprotein (AFP), Barcelona Clinic Liver Cancer (BCLC), and protein induced by vitamin K absence or antagonist II (PIVKA-II).
Figure 2
Figure 2
Survival curves according to baseline values of CYFRA 21-1 (A), AFP (B), and PIVKA-II (C). Abbreviations—alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II).
Figure 3
Figure 3
Survival curves according to risk categories. Based on the cut-off of 2.7 ng/mL for CYFRA 21-1, 20 ng/mL for AFP, and 200 mAU/mL for PIVKA-II, the low-risk category corresponded to no biomarker positivity, the intermediate risk category corresponded to the positivity to one biomarker, the high-risk category corresponded to the positivity to two biomarkers, and the very high-risk category corresponded to the positivity of all three biomarkers. Abbreviations—alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II).
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