Differential Expression and Clinical Significance of Transforming Growth Factor-Beta Isoforms in GBM Tumors

Glioblastoma (GBM) represents the most common and aggressive malignant primary brain tumors in adults. Response to standard treatment is transitory and the survival of clinical trial cohorts are little more than 14 months. GBM are characterized by excessive proliferation, invasiveness, and radio-/chemoresistance features; which are strongly upregulated by transforming growth factor-beta (TGF-beta). We hypothesized that TGF-beta gene expression could correlate with overall survival (OS) and serve as a prognostic biomarker. TGF-beta(1) and -beta(2) expression were analyzed by qPCR in 159 GBM tumor specimens. Kaplan-Meier and multivariate analyses were used to correlate expression with OS and progression-free survival (PFS). In GBM, TGF-beta(1) and -beta(2) levels were 33- and 11-fold higher respectively than in non-tumoral samples. Kaplan-Meier and multivariate analyses revealed that high to moderate expressions of TGF-beta(1) significantly conferred a strikingly poorer OS and PFS in newly diagnosed patients. Interestingly, at relapse, neither isoforms had meaningful impact on clinical evolution. We demonstrate that TGF-beta(1) is the dominant isoform in newly diagnosed GBM rather than the previously acknowledged TGF-beta(2). We believe our study is the first to unveil a significant relationship between TGF-beta(1) expression and OS or PFS in newly diagnosed GBM. TGF-beta(1) could serve as a prognostic biomarker or target affecting treatment planning and patient follow-up.