GPC3 gene expression and allelic discrimination of FZD7 gene in Egyptian patients with hepatocellular carcinoma

Amany Ramadan; Hala M Ghanem; Amal A Mohamed; Mohamed Elshobaky; Waleed El Agawy; Eman Al Hussain A Gawad; Hala H Eldeeb; Mohamed R Ezz Al Arab; Maha M Kamal

doi:10.5603/RPOR.a2023.0049

GPC3 gene expression and allelic discrimination of FZD7 gene in Egyptian patients with hepatocellular carcinoma

Rep Pract Oncol Radiother. 2023 Aug 28;28(4):485-495. doi: 10.5603/RPOR.a2023.0049. eCollection 2023.

Authors

Amany Ramadan¹, Hala M Ghanem¹, Amal A Mohamed², Mohamed Elshobaky³, Waleed El Agawy⁴, Eman Al Hussain A Gawad⁵, Hala H Eldeeb⁶, Mohamed R Ezz Al Arab⁷, Maha M Kamal¹

Affiliations

¹ Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
² Department of Biochemistry and Molecular Biology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt.
³ Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt.
⁴ Department of Infectious Diseases, Faculty of Medicine, Port Said University, Cairo, Egypt.
⁵ Department of Chemical Pathology, National Cancer Institute (NCI), Cairo University, Cairo, Egypt.
⁶ Clinical and Chemical Pathology Department, El Sahel Teaching Hospital, Cairo, Egypt.
⁷ Tropical Medicine Department, Ahmed Maher Teaching Hospital, Cairo, Egypt.

Abstract

Background: 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.

Materials and methods: 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.

Results: 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).

Conclusion: 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.

Keywords: HCC; early detection; frizzled-7; glypican-3.