Role of Elevated Serum TGF-β1 and the Common Promoter TGFB1-509C/T Polymorphism in the Development and Progression of Primary Glial Tumors and Brain Metastases.

Abstract

Background and Objectives: The role of transforming growth factor-beta1 (TGF-β1) has been widely studied in the context of carcinogenesis. It has been involved in the pathogenesis of primary brain tumors or brain metastases due to its pleiotropic effects on immune regulation and tissue homeostasis. In line with recent findings, the aim of the current study was to examine the role of circulating TGF-β1 and the -509C/T functional polymorphism (rs1800469) in the TGFB1 gene promoter in the susceptibility and progression of primary brain tumors and brain metastases among patients from the Bulgarian population. Materials and Methods: Cases with a confirmed diagnosis were genotyped by the polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). Serum TGF-β1 levels were determined by ELISA. Immunohistochemical evaluation of the expression of TGF-β1 and the TGF-β1 receptor-type II was conducted. Results: We observed that TGF-β1 serum levels correlate with the genotype and are sex-related. TGF-β1 serum levels were significantly elevated in patients compared to controls. Additionally, the T/T-genotype determined higher circulating levels of the cytokine. The same genotype determined the shorter median survival after surgery for the patients. The immunohistochemical analysis revealed a statistical tendency: cases expressing TGF-β1 in the cytoplasm had elevated levels of the cytokine in the serum compared to the negative cases. Conclusions: Overall, our results indicate a negative effect of the T-allele on the predisposition and prognosis of brain malignancies, and the genetically determined higher TGF-β1 serum levels might contribute to the worse prognosis and metastatic capacity of brain malignancies.