CHRIST: CD44-Incorporated Hepatocellular Carcinoma Risk Index Scoring Tool—A Novel Prognostic Scoring System for Hepatocellular Carcinoma Development and Aggressiveness

Abstract

CD44 has been demonstrated to play a pivotal role in regulating tumor cell progression, including hepatocellular carcinoma (HCC) development. Here, we aimed to establish a scoring system to evaluate the risk of developing HCC utilizing CD44-rs187115 SNP polymorphism. A prospective cohort of 120 individuals was enrolled in four groups: 19 non-metastatic HCC patients, 21 metastatic, 40 patients with hepatitis C-related cirrhosis, and 40 controls. Allelic discrimination of the CD44-rs187115 gene polymorphism was assessed using TaqMan genotyping assay. HCC patients with CT/CC genotypes were more likely to have aggressive malignancy compared to TT carriers. A significant correlation was noted between the existence of CT/CC genotypes and tumor size, multicentricity, infiltration, portal vein thrombosis, and metastasis. A CD44-incorporated Hepatocellular Carcinoma Risk Index Scoring Tool (CHRIST) was formulated utilizing clinical and genetic variables. A score > 3 for HCC development demonstrated 87.5% sensitivity, 72.5% specificity, and a 76% positive predictive value (PPV) and 85% negative predictive value (NPV). Furthermore, a score > 5 for HCC metastasis demonstrated 90.4% sensitivity, 68.4% specificity, a 76% PPV and 86% NPV. A similarly significant score was noted following a six-month re-evaluation. We conclude that CD44-rs187115 may serve as a reliable prognostic biomarker for HCC and that the CHRIST prognostic model is highly predictive of the development of HCC and metastatic HCC.