Influência de polimorfismos do gene TGF-β1 em pacientes com glioblastoma

O glioblastoma é o tumor mais comum e mais maligno do sistema nervoso central. Apesar de diversos avanços na medicina, estes tumores têm ainda um mau prognóstico, apresentando os pacientes uma mediana de sobrevivência de apenas 15 meses após o diagnóstico. Apesar de serem considerados muito heterogéneos, estes tumores são na maioria das vezes tratados de uma forma padronizada, o que se deve em parte à inexistência de marcadores moleculares de prognósticos fiáveis. Neste estudo, comparando amostras de sangue de indivíduos controlo (sem cancro) e pacientes com glioma, demonstrou-se que os polimorfismos -509C/T e 869T/C do TGF-β1 estão significativamente associados com o prognóstico de pacientes com glioblastoma, apresentando-se assim como um potencial biomarcador de prognóstico. Embora vários estudos tenham previamente mostrado o potencial do gene TGF-β1 como biomarcador de risco para o desenvolvimento de outros tipos de cancro e para o prognóstico desses pacientes, este é o primeiro estudo a demonstrar a sua importância no contexto de tumores cerebrais.

Autores e afiliações:
Joana Vieira de Castro¹,², Céline S. Gonçalves¹,², Sandra Costa¹,², Paulo Linhares³, Rui Vaz³, Ricardo Nabiço⁴, Júlia Amorim⁴, Marta Viana-Pereira¹,², Rui M. Reis^1,2,5, Bruno M. Costa¹,²

¹ Life and Health Sciences Research Institute, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal;

² ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Campus de Gualtar, 4710-057, Braga, Portugal;

³ Department of Neurosurgery, Hospital São João, Alameda Professor Hernâni Monteiro, 4202-451, Porto, Portugal;

⁴ Department of Oncology, Hospital de Braga, Sete Fontes – São Victor, 4710-243, Braga, Portugal;

⁵ Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Vilela, 1331 - Doutor Paulo Prata, Barretos, SP, 14780-000, Brazil

Abstract:
Transforming growth factor beta (TGF-β) plays an important role in carcinogenesis. Two polymorphisms in the TGF-β1 gene (-509C/T and 869T/C) were described to influence susceptibility to gastric and breast cancers. The 869T/C polymorphism was also associated with overall survival in breast cancer patients. In the present study, we investigated the relevance of these TGF-β1polymorphism in glioma risk and prognosis. A case-control study that included 114 glioma patients and 138 cancer-free controls was performed. Single nucleotide polymorphisms (SNPs) were evaluated by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95 % confidence intervals (95 % CI). The influence of TGF-β1 -509C/T and 869T/C polymorphisms on glioma patient survival was evaluated by a Cox regression model adjusted for patients’ age and sex and represented in Kaplan-Meier curves. Our results demonstrated that TGF-β1 gene polymorphisms -509C/T and 869T/C are not significantly associated with glioma risk. Survival analyses showed that the homozygous -509TT genotype associates with longer overall survival of glioblastoma (GBM) patients when compared with patients carrying CC + CT genotypes (OR, 2.41; 95 % CI, 1.06–5.50; p = 0.036). In addition, the homozygous 869CC genotype is associated with increased overall survival of GBM patients when compared with 869TT + TC genotypes (OR, 2.62; 95 % CI, 1.11–6.17; p = 0.027). In conclusion, this study suggests that TGF-β1 -509C/T and 869T/C polymorphisms are not significantly associated with risk for developing gliomas but may be relevant prognostic biomarkers in GBM patients.

Revista: Tumor Biology

Link: http://link.springer.com/article/10.1007/s13277-015-3343-0