Rème Thierry, Hugnot Jean-Philippe, Bièche Ivan, Rigau Valérie, Burel-Vandenbos Fanny, Prévot Vincent, Baroncini Marc, Fontaine Denys, Chevassus Hugues, Vacher Sophie, Lidereau Rosette, Duffau Hugues, Bauchet Luc, Joubert Dominique
INSERM-UM1 U1040; CHRU Montpellier, Institute of Research in Biotherapy, Montpellier, France.
PLoS One. 2013 Jun 21;8(6):e66574. doi: 10.1371/journal.pone.0066574. Print 2013.
Diffuse gliomas are incurable brain tumors divided in 3 WHO grades (II; III; IV) based on histological criteria. Grade II/III gliomas are clinically very heterogeneous and their prognosis somewhat unpredictable, preventing definition of appropriate treatment. On a cohort of 65 grade II/III glioma patients, a QPCR-based approach allowed selection of a biologically relevant gene list from which a gene signature significantly correlated to overall survival was extracted. This signature clustered the training cohort into two classes of low and high risk of progression and death, and similarly clustered two external independent test cohorts of 104 and 73 grade II/III patients. A 22-gene class predictor of the training clusters optimally distinguished poor from good prognosis patients (median survival of 13-20 months versus over 6 years) in the validation cohorts. This classification was stronger at predicting outcome than the WHO grade II/III classification (P≤2.8E-10 versus 0.018). When compared to other prognosis factors (histological subtype and genetic abnormalities) in a multivariate analysis, the 22-gene predictor remained significantly associated with overall survival. Early prediction of high risk patients (3% of WHO grade II), and low risk patients (29% of WHO grade III) in clinical routine will allow the development of more appropriate follow-up and treatments.
弥漫性胶质瘤是无法治愈的脑肿瘤，根据组织学标准分为世界卫生组织（WHO）的3个级别（II级；III级；IV级）。II/III级胶质瘤在临床上具有很大的异质性，其预后也有些不可预测，这使得难以确定合适的治疗方法。在一组65例II/III级胶质瘤患者中，基于定量聚合酶链反应（QPCR）的方法筛选出了一组具有生物学相关性的基因列表，并从中提取出与总生存期显著相关的基因特征。该基因特征将训练队列分为进展和死亡低风险与高风险两类，并且类似地将两个分别包含104例和73例II/III级患者的外部独立测试队列进行了分类。训练队列的一个由22个基因组成的分类预测指标能够在验证队列中最佳地区分预后不良和预后良好的患者（中位生存期分别为13 - 20个月和超过6年）。这种分类在预测结果方面比WHO的II/III级分类更强（P≤2.8E - 10对比0.018）。在多变量分析中，与其他预后因素（组织学亚型和基因异常）相比，这个由22个基因组成的预测指标仍然与总生存期显著相关。在临床常规中对高风险患者（占WHO II级患者的3%）和低风险患者（占WHO III级患者的29%）进行早期预测，将有助于制定更合适的随访和治疗方案。
