Khalifa Ahmed Ali, Abdeen Nermeen, Mikhael Neveen L, Elmalah Sawsan, Elshayeb Ayman
Department of Tropical Medicine, Clinical Pathology, Alexandria Faculty of Medicine, Alexandria 21433, Egypt.
Department of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC 29425, USA.
Medicines (Basel). 2022 Feb 21;9(2):14. doi: 10.3390/medicines9020014.
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.
CD44已被证明在调节肿瘤细胞进展（包括肝细胞癌（HCC）的发展）中起关键作用。在此，我们旨在建立一个评分系统，利用CD44-rs187115单核苷酸多态性来评估发生HCC的风险。120名个体的前瞻性队列被分为四组：19例非转移性HCC患者、21例转移性患者、40例丙型肝炎相关肝硬化患者和40例对照。使用TaqMan基因分型检测评估CD44-rs187115基因多态性的等位基因鉴别。与TT携带者相比，CT/CC基因型的HCC患者更有可能具有侵袭性恶性肿瘤。CT/CC基因型的存在与肿瘤大小、多中心性、浸润、门静脉血栓形成和转移之间存在显著相关性。利用临床和遗传变量制定了一个纳入CD44的肝细胞癌风险指数评分工具（CHRIST）。HCC发生评分>3显示出87.5%的敏感性、72.5%的特异性、76%的阳性预测值（PPV）和85%的阴性预测值（NPV）。此外，HCC转移评分>5显示出90.4%的敏感性、68.4%的特异性、76%的PPV和86%的NPV。在六个月的重新评估后也观察到了类似的显著评分。我们得出结论，CD44-rs187115可能作为HCC的可靠预后生物标志物，并且CHRIST预后模型对HCC和转移性HCC的发生具有高度预测性。
