In the present study, we provided evidence for increased WT1 levels and decreased E-cadherin levels in PAC cells. We also observed an inverse relationship between WT1 and E-cadherin immunohistochemistry levels in the tumor tissue. It was understood that there was an increase in WT1 and a decrease in E-cadherin levels with the progression from HGPIN to PAC in tumor progression. It was reported that the upregulation of WT1 provides an experimental basis for clinically targeted therapy of cervical cancer by suppressing cervical cancer development via miR-205
9. On the other hand, complex interactions have been identified between WT1 and IGFBP1, FBN1, SERPINA1, and 20 other genes, and it has been reported that WT1 has a new therapeutic potential in ovarian cancer
10. Another study in ovarian carcinoma revealed that WT1 plays a tumor-supporting role and increases EMT through negative modulation of ERK1/2 signaling and E-cadherin expression, and it was reported that WT1 may be a new therapeutic target that can improve the prognosis of ovarian carcinoma
11.
Many studies have evaluated the clinical significance of EMT markers at various stages of human PAC. Loss of E-cadherin staining in PAC has been reported to be associated with higher Gleason score, advanced clinical stage, and poor prognosis 12. E-cadherin expression is used to monitor the epithelial phenotype, and its loss suggests EMT 13. WT1 has been reported to be required for suppression of the epithelial phenotype during embryonic stem cell differentiation through direct transcriptional regulation of E-cadherin-related genes of EMT 14. These new insights into the molecular mechanisms regulating EMT may help in the development of cell-based therapies.
In recent years, new grade groups and American Joint Committee on Cancer stage groups have been used to predict prognosis 1. Although pathological stage seems to be one of the best prognostic factors available to date, the value of the degree of disease and clinical stage is controversial. In this study, E-cadherin immunostaining was associated with Gleason score and tumor grade, in line with the literature (Bengallo et al., 2016). However, unlike literature, significant associations were also found between E-cadherin expression and tumor stage and perineural invasion 15. Methods that allow more accurate prediction of clinical behavior are urgently needed. In this regard, investigating alternative molecular prognostic markers is now attracting significant attention.
It has been reported that E-cadherin suppresses in vitro invasion and the presence of E-cadherin staining in tumor tissue is associated with longer overall survival 16. Loss of E-cadherin has also been shown to reduce metastatic potential in invasive ductal carcinomas 17. In an overview of all data obtained, the findings suggest that E-cadherin plays opposing roles in tumor progression by suppressing cancer cell invasion.
E-cadherin, an important gene in epithelial differentiation and neoplastic transformation, represents a downstream target gene that links the roles of WT1 in differentiation and growth control 18. WT1 expression transcriptionally regulates the expression of growth control genes. WT1 is reported to be expressed in PAC epithelial cells and regulates PAC critical genes. There are reports that WT1 may also promote metastasis and suppress E-cadherin. It is reported that WT1 may activate angiogenesis in PAC cells to increase tumor growth and progression to metastatic disease 19. In this study, WT1 was not associated with the advanced pathological tumor stage. Considering the potential of WT1 to promote PAC invasion, it was evaluated that it may affect genes that promote PAC progression. Thus, it was concluded that therapies targeting WT1 in PAC may reduce metastatic spread and increase overall survival.
Consequently, it was thought that WT1 expressed in PAC epithelial cells suppresses E-cadherin and promotes progression to more advanced pathological stages, thus increasing the poor prognosis of PAC cells. It could be suggested that the potential of WT1 to promote PAC cell migration may be realized by regulating genes that stimulate the aggressive behavior of PAC.
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