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

Caviglia, Gian Paolo; Ciruolo, Michela; Olivero, Antonella; Carucci, P.; Rolle, Emanuela; Rosso, Chiara; Abate, Maria Lorena; Risso, Alessandra; Ribaldone, Davide Giuseppe; Tandoi, Francesco; Saracco, Giorgio Maria; Bugianesi, Elisabetta; Gaia, Silvia

doi:10.3390/cancers12102776

Cited by 18 publications

(13 citation statements)

References 26 publications

(26 reference statements)

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“…Serum levels of AFP and PIVKA-II were determined on the fully automated chemiluminescent enzyme immunoassay (CLEIA) system Lumipulse ® G600 II (Fujirebio Inc., Tokyo, Japan) using Lumipulse ® G AFP-N and Lumipulse ® G PIVKA-II reaction cartridges according to manufacturer's instructions. AFP concentrations were given in ng/mL, while PIVKA-II values were reported in mAU/mL [37].…”

Section: Measurement Of Serum Afp Pivka-ii and Gpc-3mentioning

confidence: 99%

Alpha-Fetoprotein, Protein Induced by Vitamin K Absence or Antagonist II and Glypican-3 for the Detection and Prediction of Hepatocellular Carcinoma in Patients with Cirrhosis of Viral Etiology

Caviglia

Ciruolo²,

Abate

et al. 2020

Cancers

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International guidelines recommend the use of ultrasound as a surveillance tool for hepatocellular carcinoma (HCC) in patients with cirrhosis, while the role of serum biomarkers is still debated. We investigated serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist II (PIVKA-II) and glypican-3 (GPC-3) diagnostic accuracy for HCC detection and prediction in patients with liver cirrhosis of viral etiology under surveillance. A total of 349 patients (200 cirrhosis and 149 HCC) were enrolled. The 200 patients with cirrhosis consisted of 114 patients still HCC-free after 36 months of follow-up and 86 patients that developed HCC after 13.8 (11.0–19.8) months. AFP, PIVKA-II and GPC-3 were measured in serum samples collected at tumor diagnosis in the 149 patients with HCC, and at the beginning of follow-up in the 200 patients with cirrhosis. The higher performance for HCC detection was observed for PIVKA-II (area under the curve (AUC) = 0.790), followed by AFP (AUC = 0.737) and GPC-3 (AUC = 0.637); the combination of AFP + PIVKA-II improved the diagnostic accuracy to AUC = 0.822. Serum PIVKA-II values, but not AFP and GPC-3, were significantly higher in the 86 cirrhotics that developed HCC compared with the 114 cirrhotics still HCC-free after 36 months of follow-up (p = 0.020). PIVKA-II ≥ 55 mAU/mL allowed to identify patients with cirrhosis at higher risk of HCC development (Log-rank test, p < 0.001; adjusted Hazard Ratio = 1.99, p = 0.001). In conclusion, the measurement of PIVKA-II in patients with cirrhosis may be useful to tailor personalized surveillance strategies.

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Section: Measurement Of Serum Afp Pivka-ii and Gpc-3mentioning

confidence: 99%

Alpha-Fetoprotein, Protein Induced by Vitamin K Absence or Antagonist II and Glypican-3 for the Detection and Prediction of Hepatocellular Carcinoma in Patients with Cirrhosis of Viral Etiology

Caviglia

Ciruolo²,

Abate

et al. 2020

Cancers

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“…The prognosis of HCC varies greatly according to the tumor stage at diagnosis and overall liver function status; therefore, a timely detection of the tumor is crucial in order to allow curative treatments and thus to improve patients’ survival [ 6 , 7 ]. According to international guidelines, surveillance for HCC should be performed in patients at risk for tumor development by means of ultrasound (US), with or without the measurement of serum alpha-fetoprotein (AFP) [ 8 , 9 ], while the Barcelona Clinic Liver Cancer (BCLC) staging system should be adopted for HCC prognostication and treatment allocation [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

The Clinical Role of Serum Epidermal Growth Factor Receptor 3 in Hepatitis C Virus-Infected Patients with Early Hepatocellular Carcinoma

Caviglia

Abate

Rolle³

et al. 2021

Biology

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Epidermal growth factor receptor 3 (ERBB3) is a surface tyrosine kinase receptor belonging to the EGFR/ERBB family, involved in tumor development and progression. We evaluated the diagnostic and prognostic value of serum ERBB3 measurement in hepatitis C virus (HCV)-infected patients with early hepatocellular carcinoma (HCC). A total of 164 HCV-infected patients (82 with cirrhosis and 82 with early HCC) were included in the study. HCC was classified according to the Barcelona Clinic Liver Cancer (BCLC) staging system. Among patients with HCC, 23 (28%) had a diagnosis of very early tumor (BCLC = 0), while 59 (62%) had a diagnosis of early HCC (BCLC = A). Median overall survival (OS) in patients with HCC was 79.2 (95% CI 51.6–124.8) months. While ERBB3 serum values were similar between patients with cirrhosis and those with HCC (p = 0.993), in the latter, serum ERBB3 ≥ 2860 RU resulted significantly and independently associated with OS (Hazard Ratio = 2.24, 95% CI 1.16–4.35, p = 0.017). Consistently, the 1-, 3-, and 5-year OS rates in patients with serum ERBB3 ≥ 2860 RU were 90% (36/40), 53% (19/36), and 28% (8/29) in comparison to patients with serum ERBB3 < 2860 RU, which were 98% (40/41), 80% (32/40), and 74% (26/35) (Log-rank test; p = 0.014). In conclusion, serum ERBB3 values resulted an independent prognostic factor of patients with early HCC and might be useful to tailor more personalized treatment strategies.

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“…CSCs were reported to be associated with tumor growth, resistance to systemic chemotherapy and epithelialmesenchymal transition, and are related to the prognosis of solid cancer patients [30]. There are a few reports that high CYFRA21-1 level is related to increased tumor size, metastasis and microvascular invasion [31]. Furthermore, high CYFRA21-1 level in HCC patients is reported to reflect Keratin 19 (K19) expression.…”

Section: Discussionmentioning

confidence: 99%

Usefulness of Circulating CYFRA21-1 in Patients as a Biomarker in Patients Taking Sorafenib or Lenvatinib for Unresectable Hepatocellular Carcinoma

Takada

Osawa

Komiyama

et al. 2021

Reports

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Background: This study investigated the impact of serum cytokeratin 19 fragment (CYFRA21-1) level on the clinical outcomes of patients with unresectable hepatocellular carcinoma (HCC) treated with sorafenib (SOR) or lenvatinib (LEN). Methods: A total of 71 cases with unresectable HCC taking SOR or LEN were included. Univariate and multivariate analyses were performed to identify the prognostic factors in patients taking SOR or LEN. Results: Among the 71 patients taking SOR or LEN, the frequency of cases showing high CYFRA21-1 levels after administration increased compared to before the administration. There was no association between the CYFRA21-1 level and the result of treatment response using modified Response Evaluation Criteria in Solid Tumors (mRECIST) 12 weeks after the administration. Univariate analysis identified a maximum intrahepatic tumor diameter of 70 mm or more, extrahepatic metastasis, baseline alpha-fetoprotein (AFP) ≥ 2000 ng/mL, baseline AFP-L3 index ≥ 15%, baseline des-gamma-carboxy prothrombin (DCP) ≥ 1000 mAU/mL, baseline CYFRA21-1 > 3.5 ng/mL, 12-week mRECIST progressive disease (PD), 12-week DCP ratio ≥ 4, 12-week CYFRA21-1 ratio ≥ 2, administration period less than 12 weeks, ALBI grade 3 at PD, and no additional treatment after discontinuation of SOR/LEN as prognostic factors. Multivariate analysis revealed that AFP-L3 index ≥ 15%, 12-week mRECIST PD, 12-week DCP ratio ≥ 4, 12-week CYFRA21-1 ratio ≥ 2, administration period less than 12 weeks, and no additional treatment after discontinuation of SOR/LEN were independent factors. Conclusions: Patients with a high CYFRA21-1 level at baseline tend to have poor prognosis, and patients with a high CYFRA21-1 ratio 12 weeks after administration have poor prognosis. Serum CYFRA21-1 measurement may have additional effects on prognostic prediction, and it may be necessary to pay close attention to the transition to the next HCC treatment in cases whose CYFRA21-1 level is high.

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

Cited by 18 publications

References 26 publications

Alpha-Fetoprotein, Protein Induced by Vitamin K Absence or Antagonist II and Glypican-3 for the Detection and Prediction of Hepatocellular Carcinoma in Patients with Cirrhosis of Viral Etiology

Alpha-Fetoprotein, Protein Induced by Vitamin K Absence or Antagonist II and Glypican-3 for the Detection and Prediction of Hepatocellular Carcinoma in Patients with Cirrhosis of Viral Etiology

The Clinical Role of Serum Epidermal Growth Factor Receptor 3 in Hepatitis C Virus-Infected Patients with Early Hepatocellular Carcinoma

Usefulness of Circulating CYFRA21-1 in Patients as a Biomarker in Patients Taking Sorafenib or Lenvatinib for Unresectable Hepatocellular Carcinoma

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