Identification of New Biomarkers Associated With IDH Mutation and Prognosis in Astrocytic Tumors Using NanoString nCounter Analysis System.
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.
Department of Pathology, School of Basic Medical Science, Peking University Health Science Center.
Ming
M
Zhang
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
Yi
Y
Pan
Department of Pathology, Sanbo Brain Hospital, Capital Medical University.
Xueling
X
Qi
Department of Pathology, School of Basic Medical Science, Peking University Health Science Center.
Yan
Y
Liu
Department of Pathology, Beijing Jishuitan Hospital, Beijing, China.
Rongfang
R
Dong
Department of Pathology, School of Basic Medical Science, Peking University Health Science Center.
Danfeng
D
Zheng
Department of Pathology, School of Basic Medical Science, Peking University Health Science Center.
Qing
Q
Chang
Department of Pathology, School of Basic Medical Science, Peking University Health Science Center.
Jing
J
Zhang
Department of Pathology, School of Basic Medical Science, Peking University Health Science Center.
Weigang
W
Fang
Department of Pathology, School of Basic Medical Science, Peking University Health Science Center.
Yanfeng
Y
Zhong
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D014408:Biomarkers, Tumor / Q000235:genetics*; D063646:Carcinogenesis; D002648:Child; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D036103:Nanotechnology; D011379:Prognosis; D016019:Survival Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D055815:Young Adult
D014408:Biomarkers, Tumor; D018841:HSP90 Heat-Shock Proteins; C493165:HSP90AB1 protein, human; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D007521:Isocitrate Dehydrogenase