Zhang Ming, Pan Yi, Qi Xueling, Liu Yan, Dong Rongfang, Zheng Danfeng, Chang Qing, Zhang Jing, Fang Weigang, Zhong Yanfeng
Department of Pathology, School of Basic Medical Science, Peking University Health Science Center.
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
Appl Immunohistochem Mol Morphol. 2018 Feb;26(2):101-107. doi: 10.1097/PAI.0000000000000396.
Isocitrate dehydrogenase (IDH) mutations have been reported as biomarkers associated with tumorigenesis and prognosis in gliomas. However, genes affected by these mutations are still under investigation. The purpose of this study is to identify new molecular biomarkers associated with IDH mutation and prognosis in astrocytic tumors, which account for the largest proportion of gliomas.
NanoString analysis was conducted on 40 astrocytic tumors. In total, 69 genes and 6 fusion genes were selected for screening. Quantitative real-time polymerase chain reaction and immunohistochemistry were used to validate the selected discriminatory genes. Kaplan-Meier survival curves and log-rank test were used to analyze the overall survival and progression-free survival.
mRNA levels of NTRK3, ERCC1, JAK2, AXL, BCL2, ESR1, HSP90AB1, TUBB3, RET, and ABCG2 were elevated in the IDH mutant group, whereas levels of POSTN and ERBB2 were elevated in the IDH wild-type group. Genes more highly expressed in the better prognosis group included NTRK3, ERCC1, ROS1, ERBB4, BCL2, CDKN2A, AXL, PI3KCA, HSP90AB1, ABCG2, JAK2, and RET. In the worse prognosis group, TIMP1, POSTN, and ERBB2 showed increased expressions. The elevated expression of HSP90AB1 was correlated with IDH mutation, long survival, and secondary glioblastomas. Elevated TIMP1 expression was related to high tumor grade and short patient survival. The results of NanoString were confirmed with quantitative real-time polymerase chain reaction and immunohistochemistry.
HSP90AB1 is related to IDH mutation and the expressions of HSP90AB1 and TIMP1 can predict prognosis in astrocytic tumors. The NanoString analysis system is a precise and reliable method to detect mRNA expression in formalin-fixed paraffin-embedded samples.
异柠檬酸脱氢酶（IDH）突变已被报道为与胶质瘤的肿瘤发生和预后相关的生物标志物。然而，受这些突变影响的基因仍在研究中。本研究的目的是在占胶质瘤比例最大的星形细胞瘤中鉴定与IDH突变和预后相关的新分子生物标志物。
对40例星形细胞瘤进行了NanoString分析。总共选择了69个基因和6个融合基因进行筛选。采用定量实时聚合酶链反应和免疫组织化学方法验证所选的鉴别基因。采用Kaplan-Meier生存曲线和对数秩检验分析总生存期和无进展生存期。
IDH突变组中NTRK3、ERCC1、JAK2、AXL、BCL2、ESR1、HSP90AB1、TUBB3、RET和ABCG2的mRNA水平升高，而IDH野生型组中POSTN和ERBB2的水平升高。在预后较好的组中表达较高的基因包括NTRK3、ERCC1、ROS1、ERBB4、BCL2、CDKN2A、AXL、PI3KCA、HSP90AB1、ABCG2、JAK2和RET。在预后较差的组中，TIMP1、POSTN和ERBB2表达增加。HSP90AB1的高表达与IDH突变、长生存期和继发性胶质母细胞瘤相关。TIMP1表达升高与高肿瘤分级和患者短生存期相关。NanoString的结果通过定量实时聚合酶链反应和免疫组织化学得到证实。
HSP90AB1与IDH突变相关，HSP90AB1和TIMP1的表达可预测星形细胞瘤的预后。NanoString分析系统是检测福尔马林固定石蜡包埋样本中mRNA表达的一种精确可靠的方法。
