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.

Background and Objectives: Glioblastoma (GBM) is the most aggressive primary tumor of the central nervous system, characterized by high invasiveness and poor prognosis. Inflammation in the tumor microenvironment, including the presence of immunosuppressive M2-macrophages (CD163+), plays a key role in disease progression. The aim of this study was to evaluate serum levels of interleukin-22 (IL-22) in Bulgarian patients with GBM and to analyze its diagnostic role, its relationship with systemic inflammatory markers (NLR), metabolic parameters, and the infiltration of CD163+ cells. Materials and Methods: The study included 41 newly diagnosed patients with GBM and 46 healthy controls. Serum IL-22 levels were measured by ELISA, and the density of CD163+ cells in the tumor tissue was analyzed immunohistochemically. Statistical analysis included Mann–Whitney test, ROC analysis, binary logistic regression, and Kaplan–Meier survival analysis. Results: GBM patients showed significantly higher levels of IL-22 compared to healthy controls (p = 0.001). ROC analysis demonstrated moderate diagnostic ability of IL-22 (AUC = 0.713), with high levels being a potential risk factor for the disease (OR= 2.51). A weak inverse correlation was found between IL-22 and neutrophil-to-lymphocyte ratio (NLR) (p = 0.048). Although IL-22 levels alone did not affect overall survival, patients with high levels of the cytokine and dense stromal infiltration of CD163+ macrophages tended to have shorter overall survival (p = 0.080). Conclusions: IL-22 is a potential diagnostic biomarker, probably reflecting the systemic inflammatory response in GBM. Its prognostic value might be contextually dependent on the tumor microenvironment, as high levels of IL-22 in combination with immunosuppressive macrophages may contribute to a more aggressive course of the disease.