Department of Pharmacology, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Department of Surgery, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Int J Mol Sci. 2018 Apr 8;19(4):1113. doi: 10.3390/ijms19041113.
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-β). We hypothesized that TGF-β gene expression could correlate with overall survival (OS) and serve as a prognostic biomarker. TGF-β₁ and -β₂ 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-β₁ and -β₂ 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-β₁ 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-β₁ is the dominant isoform in newly diagnosed GBM rather than the previously acknowledged TGF-β₂. We believe our study is the first to unveil a significant relationship between TGF-β₁ expression and OS or PFS in newly diagnosed GBM. TGF-β₁ could serve as a prognostic biomarker or target affecting treatment planning and patient follow-up.
胶质母细胞瘤（GBM）是成人中最常见且侵袭性最强的恶性原发性脑肿瘤。对标准治疗的反应是短暂的，临床试验队列的生存时间仅超过 14 个月。GBM 的特征是过度增殖、侵袭性和放射/化学耐药性特征；这些特征受到转化生长因子-β（TGF-β）的强烈上调。我们假设 TGF-β 基因表达可以与总生存期（OS）相关，并作为预后生物标志物。在 159 个 GBM 肿瘤标本中通过 qPCR 分析 TGF-β₁和-β₂的表达。使用 Kaplan-Meier 和多变量分析来将表达与 OS 和无进展生存期（PFS）相关联。在 GBM 中，TGF-β₁和-β₂的水平分别比非肿瘤样本高 33 倍和 11 倍。Kaplan-Meier 和多变量分析显示，TGF-β₁的高至中度表达显著导致新诊断患者的 OS 和 PFS 明显变差。有趣的是，在复发时，两种同工型都对临床进展没有意义。我们证明，TGF-β₁是新诊断的 GBM 中的主要同工型，而不是先前公认的 TGF-β₂。我们认为我们的研究首次揭示了新诊断的 GBM 中 TGF-β₁表达与 OS 或 PFS 之间的显著关系。TGF-β₁可以作为影响治疗计划和患者随访的预后生物标志物或靶标。
