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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.
Highlights
Despite the significant decline in hepatitis C virus (HCV) cases since the introduction of directly acting antivirals, the CDC estimates that nearly 2.4 million Americans were living with HCV infection in 2018 [1]
Liver-specific cancer stem cells (CSCs) have been isolated in hepatocellular carcinoma (HCC) by several cell-surface antigens including several clusters of differentiation (CD), such as CD44, CD133, and CD90
CD44-positive cells have been suggested to be involved in the epithelial-mesenchymal transition (EMT), a genetic process associated with cancer invasion and metastasis [8,9,10,11]
Summary
Despite the significant decline in hepatitis C virus (HCV) cases since the introduction of directly acting antivirals, the CDC estimates that nearly 2.4 million Americans were living with HCV infection in 2018 [1]. The available data suggest that hepatic cancer stem cells (CSCs) are incorporated in the development of HCC. Liver-specific CSCs have been isolated in HCC by several cell-surface antigens including several clusters of differentiation (CD), such as CD44, CD133, and CD90. The CD44 role in human cancer metastasis (and a possible therapeutic effect) was studied in several cancer cells, but CD44 gene single-nucleotide polymorphism (SNP) and its role in HCC development and clinical features remain poorly investigated [13,14,15,16,17]. We aimed to study a common SNP in the 3 untranslated region (UTR) of CD44 (identified as rs187115) and incorporate it into a scoring system to evaluate HCC behavior and aggressiveness
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