Center for Neurosurgical Outcomes Research, Department of Neurosurgery, Cedars-Sinai Medical Center, 8631 W Third St, Suite 800E, Los Angeles, CA 90048, USA.
Neuro Oncol. 2013 Jan;15(1):104-11. doi: 10.1093/neuonc/nos272. Epub 2012 Oct 31.
We investigated whether high levels of activated mitogen-activated protein kinase (p-MAPK) were associated with poor survival among patients with newly diagnosed glioblastoma during the temozolomide era. Nuclear p-MAPK expression of 108 patients with GBM was quantified and categorized in the following levels: low (0%-10%), medium (11%-40%), and high (41%-100%). Independent predictors of overall survival were determined using a multivariate Cox proportional hazards model. Our study included 108 patients with newly diagnosed GBM. Median age was 65 years, and 74% had high Karnofsky performance status (KPS ≥ 80). Median overall survival among all patients was 19.5 months. Activated MAPK expression levels of <10%, 11%-40%, and ≥ 41% were observed in 33 (30.6%), 37 (34.3%), and 38 (35.2%) patients, respectively. Median survival for low, medium, and high p-MAPK expression was 32.4, 18.2, and 12.5 months, respectively. Multivariate analysis showed 2.4-times hazard of death among patients with intermediate p-MAPK than low p-MAPK expression (hazard ratio [HR], 2.4; P = .02); high-expression patients were 3.9 times more likely to die, compared with patients with low p-MAPK (HR, 3.9; P = .007). Patients aged ≥ 65 years (HR, 2.8; P = .002) with KPS < 80 (HR, 3.1; P = .0003) and biopsy or partial resection (HR, 1.9; P = .02) had higher hazard of death. MGMT and PTEN expression were not associated with survival differences. This study provides quantitative means of evaluating p-MAPK in patients with GBM. It confirms the significant and independent prognostic relevance of p-MAPK in predicting survival of patients with GBM treated in the temozolomide era and highlights the need for therapies targeting the p-MAPK oncogenic pathway.
我们研究了在替莫唑胺治疗时代，新诊断为胶质母细胞瘤患者中，高活性丝裂原活化蛋白激酶（p-MAPK）水平是否与不良预后相关。我们对 108 例 GBM 患者的核 p-MAPK 表达进行了定量，并分为以下水平：低（0%-10%）、中（11%-40%）和高（41%-100%）。采用多变量 Cox 比例风险模型确定总生存期的独立预测因素。我们的研究包括 108 例新诊断的 GBM 患者。中位年龄为 65 岁，74%的患者 Karnofsky 表现状态（KPS≥80）良好。所有患者的中位总生存期为 19.5 个月。低、中、高 MAPK 表达水平分别为<10%、11%-40%和≥41%的患者分别为 33（30.6%）、37（34.3%）和 38（35.2%）例。低、中、高 p-MAPK 表达的中位生存时间分别为 32.4、18.2 和 12.5 个月。多变量分析显示，p-MAPK 表达水平为中间值的患者死亡风险是低水平患者的 2.4 倍（风险比[HR]，2.4；P=0.02）；与低 p-MAPK 表达的患者相比，高表达患者死亡的可能性增加 3.9 倍（HR，3.9；P=0.007）。年龄≥65 岁（HR，2.8；P=0.002）、KPS<80（HR，3.1；P=0.0003）和活检或部分切除术（HR，1.9；P=0.02）的患者死亡风险更高。MGMT 和 PTEN 表达与生存差异无关。本研究提供了一种定量评估胶质母细胞瘤患者 p-MAPK 的方法。它证实了 p-MAPK 在预测替莫唑胺治疗时代胶质母细胞瘤患者生存中的显著和独立的预后相关性，并强调了靶向 p-MAPK 致癌途径的治疗方法的必要性。
