The Role and Significance of Wnt5a in Regulating Epithelial–Mesenchymal Transition in Endometrioid Adenocarcinoma

Abstract

Purpose

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

Data Sharing Statement

No additional data are available.

Ethics Approval and Informed Consent

Informed consent was obtained from all patients and their families. The study was approved by the Ethics Committee of the First Affiliated Hospital of Bengbu Medical College (NO. 2020057).

Author Contributions

NNY prepared the manuscript and contributed to data analysis and manuscript revision. HCC, YCH,and XXS assisted in cytological and histological experiments and directly participated in the revision of sections regarding the cytological experiments.. PPY, SZ, and WTY participate in the collection and interpretation of clinical data, and provide writing assistance related to format and grammar. ZZF and NL guided the first draft and revised draft of the paper, made pathological diagnosis and supervised the study. All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.