Cancer Management and Research (Aug 2021)
The Role and Significance of Wnt5a in Regulating Epithelial–Mesenchymal Transition in Endometrioid Adenocarcinoma
Abstract
Ningning Yang,1,2 Hongchun Chen,1,2 Yuchen Huang,1,2 Xuexue Song,3 Panpan Yang,4 Shan Zhang,5 Wentian Yan,1,2 Nan Li,1,2 Zhenzhong Feng1,2 1Department of Pathology, First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, People’s Republic of China; 2Department of Pathology, Bengbu Medical College, Bengbu, 233000, People’s Republic of China; 3Department of Pathology, First Affiliated Hospital of University of Science and Technology of China, Hefei, 230000, People’s Republic of China; 4Department of Pathology, Second Affiliated Hospital of Anhui Medical University, Hefei, 230000, People’s Republic of China; 5Department of Pathology, Second People’s Hospital of Hefei, Hefei, 230000, People’s Republic of ChinaCorrespondence: Zhenzhong Feng; Nan LiDepartment of Pathology, First Affiliated Hospital of Bengbu Medical College, No. 287 Changhuai Road, Bengbu, Anhui Province, People’s Republic of ChinaTel +86 15055289508Email [email protected]; [email protected]: As a non-classical ligand of Wnt, the abnormal regulation of Wnt5a contributes to the progression of malignant tumors; however, its effects differ depending on tumor type. Here, we evaluated the expression and significance of Wnt5a in endometrioid adenocarcinoma and its relationship with epithelial–mesenchymal transition (EMT)-related proteins.Patients and Methods: Immunohistochemical streptavidin-peroxidase method and reverse transcription polymerase chain reaction (RT-PCR) method were used to analyze the expression and correlation of Wnt5a, and EMT-related protein β-catenin, E-cadherin and enhancer of zeste homolog 2 (EZH2) in endometrial cancer tissues and cell samples of each group.Results: The expression of Wnt5a and E-cadherin decreased in the following order, normal endometrium > atypical hyperplasia endometrium > endometrioid adenocarcinoma. In contrast, the expression of β-catenin and EZH2 increased gradually. Moreover, Wnt5a expression was associated with the degree of tissue differentiation, International Federation of Gynecology and Obstetrics (FIGO) stage, and lymph node metastasis (all P< 0.05). Wnt5a expression was also negatively correlated with β-catenin and EZH2 expression and positively correlated with E-cadherin expression. RT-PCR results further indicated that E-cadherin mRNA expression was upregulated in a Wnt5a-overexpressing Ishikawa cell line compared to cells transfected with an empty vector or negative control cells (P< 0.01). Furthermore, the expression of EZH2 and β-catenin mRNA was downregulated in overexpressing cells compared to empty vector and negative control cells (P< 0.01).Conclusion: Wnt5a may elicit a suppressive effect on endometrioid adenocarcinoma by inhibiting EMT. This study provides a theoretical basis for the pathological diagnosis and targeted therapy of endometrioid adenocarcinoma and extends our understanding of the Wnt5a signaling pathway.Keywords: endometrioid adenocarcinoma, Wnt5a, epithelial–mesenchymal transition, immunohistochemistry
