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Identification of New Biomarkers Associated With IDH Mutation and Prognosis in Astrocytic Tumors Using NanoString nCounter Analysis System

Zhang, Ming, PhD*; Pan, Yi, PhD; Qi, Xueling, MSc; Liu, Yan, PhD*; Dong, Rongfang, PhD§; Zheng, Danfeng, PhD*; Chang, Qing, PhD*; Zhang, Jing, PhD*; Fang, Weigang, PhD*; Zhong, Yanfeng, BSc*

Applied Immunohistochemistry & Molecular Morphology: February 2018 - Volume 26 - Issue 2 - p 101–107
doi: 10.1097/PAI.0000000000000396
Research Articles

Background: 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.

Materials and Methods: 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.

Results: 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.

Conclusions: 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.

*Department of Pathology, School of Basic Medical Science, Peking University Health Science Center

Department of Pathology, Sanbo Brain Hospital, Capital Medical University

§Department of Pathology, Beijing Jishuitan Hospital, Beijing, China

Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong

Supported by grants to W.G.F. from National Natural Science Foundation of China (81321003).

The authors declare no conflict of interest.

Reprints: Yanfeng Zhong, BSc, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China (e-mail:

Received February 22, 2016

Accepted April 21, 2016

Copyright 2018 Wolters Kluwer Health, Inc. All rights reserved.