MCAM is a prognostic serum biomarker in patients with liver cirrhosis and HCC

Chronic liver diseases are a major public health burden. The rising incidence of patients with liver cirrhosis and hepatocellular carcinoma (HCC) emphasizes the need for non-invasive markers that predict poor prognosis. Melanoma cell adhesion molecule (MCAM) is a cell surface adhesion molecule expressed by diverse cell types. MCAM cleavage by metalloproteinases, known to be enriched in fibrotic and malignant diseases, results in release of a soluble form into the serum. The aim of this study was to evaluate soluble MCAM as a prognostic serum biomarker in patients with chronic liver disease. Interestingly, we found serum levels of MCAM to be highly dysregulated in patients with liver cirrhosis and HCC (n=302 and n=54, p<0.0001, F-test, respectively). Corroborating an association of MCAM release with fibrogenesis and carcinogenesis, serum levels correlated with both liver stiffness by transient elastography in patients with liver cirrhosis (p=0.02) and alpha-fetoprotein (AFP) level in patients with HCC (p=0.05). Moreover, MCAM serum levels showed an association with overall survival in both study cohorts. Thus, patients with HCC and MCAM serum levels>1216 ng/ml showed a more than 14 times higher risk of death within 5 year’s follow up compared to patients with lower levels (p=0.001, log-rank test). Collectively, our study reveals MCAM as a novel prognostic serum biomarker in patients with liver cirrhosis and patients with HCC.