Department of Neurosurgery, University Hospital Olomouc, I.P. Pavlova 6, 779 00 Olomouc, Czech Republic.
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc, Hnevotinska 5, 779 00 Olomouc, Czech Republic.
Curr Oncol. 2021 Mar 21;28(2):1280-1293. doi: 10.3390/curroncol28020122.
This prospective population-based study on a group of 132 resected IDH-wildtype (IDH-wt) glioblastoma (GBM) patients assesses the prognostic and predictive value of selected genetic biomarkers and clinical factors for GBM as well as the dependence of these values on the applied therapeutic modalities. The patients were treated in our hospital between June 2006 and June 2015. Clinical data and tumor samples were analyzed to determine the frequencies of TP53, MDM2, EGFR, RB1, BCR, and CCND1 gene aberrations and the duplication/deletion statuses of the 9p21.3, 1p36.3, 19q13.32, and 10p11.1 chromosome regions. Cut-off values distinguishing low (LCN) and high (HCN) copy number status for each marker were defined. Additionally, MGMT promoter methylation and IDH1/2 mutation status were investigated retrospectively. Young age, female gender, Karnofsky scores (KS) above 80, chemoradiotherapy, TP53 HCN, and CCND1 HCN were identified as positive prognostic factors, and smoking was identified as a negative prognostic factor. Cox proportional regression models of the chemoradiotherapy patient group revealed TP53 HCN and CCND1 HCN to be positive prognostic factors for both progression-free survival and overall survival. These results confirmed the influence of key clinical factors (age, KS, adjuvant oncotherapy, and smoking) on survival in GBM IDH-wt patients and demonstrated the prognostic and/or predictive importance of CCND1, MDM2, and 22q12.2 aberrations.
本前瞻性基于人群的研究纳入了 132 例 IDH 野生型（IDH-wt）胶质母细胞瘤（GBM）患者，评估了选定的遗传生物标志物和临床因素对 GBM 的预后和预测价值，以及这些因素对所应用治疗方式的依赖性。这些患者于 2006 年 6 月至 2015 年 6 月在我院接受治疗。分析了临床数据和肿瘤样本，以确定 TP53、MDM2、EGFR、RB1、BCR 和 CCND1 基因异常以及 9p21.3、1p36.3、19q13.32 和 10p11.1 染色体区域的重复/缺失状态的频率。定义了区分每个标志物低（LCN）和高（HCN）拷贝数状态的截止值。此外，还回顾性研究了 MGMT 启动子甲基化和 IDH1/2 突变状态。年轻、女性、卡氏评分（KS）＞80、放化疗、TP53 HCN 和 CCND1 HCN 被鉴定为阳性预后因素，而吸烟被鉴定为阴性预后因素。放化疗患者组的 Cox 比例回归模型显示，TP53 HCN 和 CCND1 HCN 是无进展生存期和总生存期的阳性预后因素。这些结果证实了关键临床因素（年龄、KS、辅助抗肿瘤治疗和吸烟）对 GBM IDH-wt 患者生存的影响，并表明 CCND1、MDM2 和 22q12.2 异常具有预后和/或预测意义。
