Identification of Cyclase-Associated Protein-2 as a Novel Biomarker for Early-Stage Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is an aggressive deadly cancer with few therapeutic options mostly limited for early-stage HCC. Unfortunately, alphafetoprotein (AFP) has a limited performance, especially in early-stage HCC. Objectives: to investigate plasma levels of Cyclaseassociated protein-2 (CAP2) as a new biomarker and evaluate its role in detecting early-stage and AFP-negative HCC Egyptian patients. Methods: Plasma CAP2 and AFP levels in 150 HCC, 150 cirrhotic patients, 150 healthy controls. Correlation with tumor behavior, the area under the curve (AUC), sensitivity, specificity, and diagnostic accuracy were analyzed. Results: Plasma CAP2 and AFP levels were significantly elevated in HCC patients than liver cirrhosis and controls. Only plasma CAP2 levels significantly correlated with clinico-pathological characteristics of HCC (BCLC, histological and clinical stages) but not correlated with patient's age, gender, viral infection status or AFP levels. Compared to AFP, CAP2 had significantly higher AUC: 0.86 (0.79-0.93) vs. 0.75 (0.65-0.85), Sensitivity: 81.5% vs. 62% in all HCCs and significantly higher AUC: 0.80 (0.72-0.89) vs. 0.68 (0.58-0.79, Sensitivity: 80.5% vs. 43.1% in earlystage HCC. Moreover, the combined diagnostic value of both CAP2+AFP was statistically significantly better than either CAP2 or AFP alone. Also, CAP2 could predict 82.4% of AFP-negative HCCs [AUC: 0.85 (0.77-0.92)] and 73.5% of AFP-negative early-stage HCCs [AUC: 0.80 (0.72-0.88)]. Conclusion: Compared with AFP, CAP2 was significantly elevated in HCC patients with higher sensitivity and AUC especially for early-stage HCC. Moreover, CAP2 was significantly correlated with the clinico-pathological features of HCC. CAP2 could be a novel biomarker predicting early-stage, AFP-negative, and AFP-negative early-stage HCC patients.