Department of Neurosurgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Clin Pathol. 2018 Aug;71(8):702-707. doi: 10.1136/jclinpath-2018-205000. Epub 2018 Mar 17.
To identify biomarkers for accurate classification of glioma.
We evaluated the heat shock protein 27 (Hsp27), phosphorylated Hsp27 (p-Hsp27), ATRX and IDH1proteins using immunohistochemistry in 421 glioma tissues. The χ test was used to assess the relationship between molecular alterations and clinico-pathological parameters. Kaplan-Meier survival curves were constructed, and differences were detected by the log-rank test.
We found that Hsp27 and p-Hsp27 were mainly expressed in aggressive astrocytic gliomas. However, neither Hsp27 nor p-Hsp27 expression was related to survival time for any grade of glioma. Interestingly, p-Hsp27 was mutually exclusive with ATRX loss (ATRX) and the IDH1 mutation, except for one case of anaplastic astrocytoma. We classified glioblastomas (GBMs) into three subtypes: ATRX/IDH1, high p-Hsp27 expression (p-Hsp27) and none of these three markers. ATRX/IDH1showed the longest median survival (19.6 months). The prognostic difference between p-Hsp27 and none of these three markers was significant (15.0 vs 13.1 months, P=0.045). Moreover, p-Hsp27 predicted better sensitivity for standard therapy among GBMs without the IDH1 mutation and ATRX loss (26.3 vs 15.5 months, P=0.008).
p-Hsp27 is a novel biomarker of glioma and might have important clinical value for further classification of patients with wild-type IDH1 and normal ATRX expression, for evaluating prognosis and for guidance for adjuvant therapy.
鉴定用于准确分类脑胶质瘤的生物标志物。
我们使用免疫组织化学方法评估了 421 例脑胶质瘤组织中的热休克蛋白 27（Hsp27）、磷酸化 Hsp27（p-Hsp27）、ATR 和 IDH1 蛋白。χ 检验用于评估分子改变与临床病理参数之间的关系。Kaplan-Meier 生存曲线构建，采用对数秩检验检测差异。
我们发现 Hsp27 和 p-Hsp27 主要在侵袭性星形细胞瘤中表达。然而，Hsp27 和 p-Hsp27 的表达均与任何级别胶质瘤的生存时间无关。有趣的是，p-Hsp27 与 ATRX 缺失（ATRX）和 IDH1 突变互斥，除了一例间变性星形细胞瘤。我们将胶质母细胞瘤（GBM）分为 3 种亚型：ATRX/IDH1、高 p-Hsp27 表达（p-Hsp27）和这 3 种标志物均无。ATRX/IDH1 显示最长的中位生存时间（19.6 个月）。p-Hsp27 与这 3 种标志物均无之间的预后差异有统计学意义（15.0 与 13.1 个月，P=0.045）。此外，p-Hsp27 预测无 IDH1 突变和 ATRX 缺失的 GBM 患者对标准治疗的敏感性更好（26.3 与 15.5 个月，P=0.008）。
p-Hsp27 是一种新型脑胶质瘤生物标志物，对于进一步分类 IDH1 野生型和 ATRX 表达正常的患者、评估预后和指导辅助治疗可能具有重要的临床价值。
