Pankreas Kanserinde MUC1, MUC4, MUC16 Molekülleri ile Treg Hücreleri ve Epitelyal-Mezenkimal Transizyon Arasındaki İlişki

Abstract

Pancreatic cancer has a poor prognosis due to its increased invasion and metastasis capacity. Transmembrane mucins normally have as their functions to protect the epithelial tissues but their expression level is has been found to increase in tumors. Epithelial-mesenchymal transition (EMT) plays an important role to understand the potential mechanisms for tumor progression and metastasis. Treg cells are critical for maintaining immune tolerance, but they can also impede antitumor immune responses. Treg cells promote tumor progression and metastasis via their immune-suppressive functions. The study aims to investigate the relationship between transmembrane mucins (MUC1, MUC4, MUC16) and the expression levels of EMT molecules (E-Cadherin, N-Cadherin, TWIST) and FOXP3+ Treg cells in the microenvironment. Also in this study, it was aimed to determine the relationship between the expression levels of molecules and clinicopathological findings. Archive tissues of 50 (18F) pancreatic cancer patients were included in the study, the mean age of the patients was 69.7 (40-94). The analysis was performed by real-time PCR (Q-PCR) and immunohistochemistry (IHC). The relative gene expression levels in tissues were calculated using the 2-∆∆Ct method. The relations between expression levels and tumor differentiation, TNM stage, lymph node metastasis, and metastasis were investigated. There was no significant difference in the expression levels of MUC1 in the tumor. The gene and molecular expression levels of MUC4 and MUC16 were found to be increased in tumor tissue compared to normal tissue (p <0.05) and positive correlation was found between them (p <0.001). FOXP3 gene and molecule expression levels were found to be significantly increased in tumor tissues (p <0.05). Loss of gene and molecule expression, an increase of N-cadherin and TWIST expression were analyzed in the tumor. EMT was detected in 24 patients (48%). E-Cadherin and TWIST gene and molecule expression changes were found significant in the tumor (p <0.05). There was a significant correlation between the increased expression of FOXP3 and MUC16 in the tumor and the TNM stage (p <0.001), and the high expression of these genes in the early stages was remarkable. The levels of FOXP3 gene expression increased in EMT-active patients. In addition, MUC16 gene expression was found to be significant between patients serum levels of CA 19-9 (p <0.05). In conclusion, our findings on MUC16, FOXP3 and EMT expressed in pancreatic cancer suggest that MUC16 and Treg cells may support EMT. Further studies can be planned to explain the possible mechanisms of interaction of these genes and these mechanisms can play a role in determining new target molecules in pancreatic cancer.