Ramadan Amany, Ghanem Hala M, Mohamed Amal A, Elshobaky Mohamed, El Agawy Waleed, Gawad Eman Al Hussain A, Eldeeb Hala H, Ezz Al Arab Mohamed R, Kamal Maha M
Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
Department of Biochemistry and Molecular Biology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt.
Rep Pract Oncol Radiother. 2023 Aug 28;28(4):485-495. doi: 10.5603/RPOR.a2023.0049. eCollection 2023.
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide, and especially in Egypt. Early diagnosis of HCC greatly improves the survival and prognosis of patients. Low sensitivity and specificity of alpha-fetoprotein (AFP) has led to the demand for novel biomarkers of HCC. The aim of the present study was to evaluate the validity of frizzled-7 (FZD7) and glypican-3 (GPC3) gene expression as potential biomarkers for HCC early diagnosis, and to investigate the association between FZD7 rs2280509 polymorphism and HCC risk.
Quantification of FZD7 and GPC3 gene expression by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay, and genotyping FZD 7 (rs2280509 SNP) gene polymorphism using RT-PCR.
The current results revealed that FZD7 gene expression had a greater area under the curve (AUC) for identifying HCC than GPC3 gene expression and AFP levels. The combination of the three markers as a panel showed a better diagnostic performance with a greater AUC than any of the single markers alone (p < 0.05). The FZD7 rs2280509 polymorphism (CT) was found to be significantly associated with an increased risk of HCC. The CT genotype and T allele were significantly more prevalent in the HCC group compared to either the cirrhosis (p = 0.03) or control groups (p = 0.0009 and 0.002; respectively).
FZD7 and GPC3 gene expressions have a complementary role in early HCC detection, with a greater diagnostic sensitivity and accuracy than AFP. In addition, FZD7 rs2280509 polymorphism is significantly associated with an increased risk of HCC in the Egyptian population.
肝细胞癌（HCC）是全球尤其是埃及癌症相关死亡的第二大主要原因。HCC的早期诊断可显著提高患者的生存率和预后。甲胎蛋白（AFP）的低敏感性和特异性导致了对HCC新型生物标志物的需求。本研究的目的是评估卷曲蛋白-7（FZD7）和磷脂酰肌醇蛋白聚糖-3（GPC3）基因表达作为HCC早期诊断潜在生物标志物的有效性，并研究FZD7 rs2280509多态性与HCC风险之间的关联。
通过实时定量逆转录聚合酶链反应（qRT-PCR）测定法对FZD7和GPC3基因表达进行定量，并使用RT-PCR对FZD 7（rs2280509 SNP）基因多态性进行基因分型。
目前的结果显示，与GPC3基因表达和AFP水平相比，FZD7基因表达在识别HCC方面具有更大的曲线下面积（AUC）。作为一个组合的这三种标志物显示出比任何单个标志物更好的诊断性能，AUC更大（p < 0.05）。发现FZD7 rs2280509多态性（CT）与HCC风险增加显著相关。与肝硬化组（p = 0.03）或对照组（分别为p = 0.0009和0.002）相比，CT基因型和T等位基因在HCC组中显著更常见。
FZD7和GPC3基因表达在HCC早期检测中具有互补作用，诊断敏感性和准确性高于AFP。此外，FZD7 rs2280509多态性与埃及人群中HCC风险增加显著相关。
