Predictive Value of Serum CYFRA 21-1 and CK19-2G2 for Tumor Aggressiveness and Overall Survival in Hepatitis C-Related Hepatocellular Carcinoma Among Egyptians: A Prospective Study

Mohamed Yousry Taher; Ehab Mostafa Hassouna; Abeer Shawky El-Hadidi; Omar Sameh El-Aassar; Mohamed Fathy Bakosh

doi:10.1007/s12029-023-01012-4

Predictive Value of Serum CYFRA 21-1 and CK19-2G2 for Tumor Aggressiveness and Overall Survival in Hepatitis C-Related Hepatocellular Carcinoma Among Egyptians: A Prospective Study

J Gastrointest Cancer. 2024 Jan 17. doi: 10.1007/s12029-023-01012-4. Online ahead of print.

Authors

Mohamed Yousry Taher¹, Ehab Mostafa Hassouna¹, Abeer Shawky El-Hadidi², Omar Sameh El-Aassar³, Mohamed Fathy Bakosh⁴

Affiliations

¹ Hepatobiliary Unit, Internal Medicine Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
² Clinical and Chemical Pathology Department, Faculty of Medicine, Alexandria University, Egypt.
³ Diagnostic and Interventional Radiology Department, Faculty of Medicine, Alexandria University, Egypt.
⁴ Hepatobiliary Unit, Internal Medicine Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt. M_fathy160@alexmed.edu.eg.

PMID: 38231289
DOI: 10.1007/s12029-023-01012-4

Abstract

Purpose: Cytokeratin 19 fragment 21-1 (CYFRA 21-1) and cytokeratin 19 fragment 2G2 (CK 19-2G2) are two soluble fragments of cytokeratin 19 (CK 19) that can be detected in serum. CK 19-positive hepatocellular carcinoma (HCC) is characterized by an aggressive behavior and a poor outcome. This study aimed to assess the prognostic value of serum CYFRA 21-1 and CK 19-2G2 in predicting tumor aggressiveness and overall survival (OS) in patients with hepatic C virus (HCV)-related HCC.

Methods: The current study included 138 patients with HCV-related HCC recruited from the Hepatobiliary and Interventional Radiology Units at Alexandria's main university hospitals and 40 healthy individuals as controls. Patients were assessed for clinical, radiological tumor characteristics, and aggressiveness index. Baseline serum CYFRA 21-1 and CK 19-2G2 levels were measured by enzyme-linked immunosorbent assay.

Results: Elevated CYFRA 21-1 levels were associated with tumors size ≥ 5 cm (p < 0.001), malignant portal vein thrombosis (mPVT) (p < 0.001), distant metastasis (p = 0.030), ill-defined/infiltrative pattern (p = 0.010), and aggressiveness index > 4 (p = 0.045). Elevated CK19-2G2 levels were not associated with any clinical or radiological characteristics. Either or both elevated serum CYFRA 21-1 and CK 19-2G2 in combination with alpha-feto protein (AFP) ≥ 400 ng/ml have a better predictability for mPVT and ill-defined/infiltrative patterns (sensitivity (10-25%) and specificity (96-100%)). Elevated levels of CYFRA 21-1, CK 19-2G2, or AFP ≥ 400 ng/ml were associated with decreased 1-year OS.

Conclusions: Either or both elevated serum CYFRA 21-1 and CK 19-2G2 levels when added to AFP ≥ 400 ng/ml are specific but less sensitive biomarkers for predicting tumor aggressiveness. These biomarkers can be used independently to predict reduced 1-year OS in Egyptian patients with HCV-related HCC.

Keywords: Aggressiveness index; CK 19-2G2; CYFRA 21–1; Cytokeratin 19; Hepatocellular carcinoma; Overall survival.