Evaluation the Role of Lipocalin 2 as a New Non-Invasive Diagnostic Marker for Hepatocellular Carcinoma in Egyptian Cirrhotic Patients

Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer globally and a major health challenge in Egypt, where it ranks as fourth most prevalent cancer. Current diagnostic approaches, including serum alpha-fetoprotein (AFP) and imaging, have limitations, particularly in early detection. Lipocalin-2 (LCN2), a protein secreted during hepatic damage, shows promise as a novel non-invasive biomarker for HCC diagnosis. Objective: This study aimed to evaluate diagnostic potential of serum LCN2 in distinguishing HCC from liver cirrhosis and healthy controls in an Egyptian cohort. Patients and methods: A case-control study was conducted on 96 participants: 32 HCC patients, 32 cirrhotic patients without HCC, and 32 healthy controls. Serum LCN2 levels were measured using enzyme-linked immunosorbent assay (ELISA). Comparative and diagnostic performance analyses were performed using ANOVA and ROC curve analysis. Results: LCN2 levels were significantly higher in HCC patients 293 (140–445 ng/L) compared to cirrhotic patients 129 (20–239 ng/L, P < 0.001) and healthy controls 53 (38–68 ng/L, P < 0.001). ROC curve analysis demonstrated a sensitivity and specificity of 96.87% each and an accuracy of 98.4% at a cutoff of >160 ng/L. Serum AFP was also elevated in HCC patients 2737 (0–22303 ng/mL, P < 0.05), but LCN2 exhibited superior diagnostic performance. Conclusion: Serum LCN2 is a highly sensitive and specific biomarker for HCC diagnosis. Combined with AFP, it could enhance early detection in surveillance programs. Further studies are recommended to validate its role in diverse populations and clinical settings.