title: MicroRNA profiling of Chinese primary glioblastoma reveals a temozolomide-chemoresistant subtype.
abstract: Accumulating evidence demonstrates that defining molecular subtypes based on objective genetic alterations may permit a more rational, patient-specific approach to molecular targeted therapy across various cancers. The objective of this study was to subtype primary glioblastoma (pGBM) based on MicroRNA (miRNA) profiling in Chinese population. Here, miRNA expression profiles from 82 pGBM samples were analyzed and 78 independent pGBM samples were used for qRT-PCR validation. We found that two distinct subgroups with different prognosis and chemosensitivities to temozolomide (TMZ) in Chinese pGBM samples. One subtype is TMZ chemoresistant (termed the TCR subtype) and confers a poor prognosis. The other subtype is TMZ-chemosensitive (termed the TCS subtype) and confers a relatively better prognosis compared with the TCR subtype. A classifier consisting of seven miRNAs was then identified (miR-1280, miR-1238, miR-938 and miR-423-5p (overexpressed in the TCR subtype); and let-7i, miR-151-3p and miR-93 (downregulated in the TCR subtype)), which could be used to assign pGBM samples to the corresponding subtype. The classifier was validated using both internal and external samples. Meanwhile, the genetic alterations of the TCR and TCS subtypes were also analyzed. The TCR subtype was characterized by no IDH1 mutation, and EGFR and Ki-67 overexpression. The TCS subtype displayed the opposite situation. Taken together, the results indicate a distinct subgroup with poor prognosis and TMZ-chemoresistance.
authors: Beijing Neurosurgical Institute, Capital Medical University, Beijing, PR China.|Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors: Wei
authors: W
authors: Yan
authors: Beijing Neurosurgical Institute, Capital Medical University, Beijing, PR China.|Beijing Institute for Brain Disorders, Brain Tumor Center, Beijing, PR China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, PR China.
authors: Yanwei
authors: Y
authors: Liu
authors: Beijing Neurosurgical Institute, Capital Medical University, Beijing, PR China.|Beijing Institute for Brain Disorders, Brain Tumor Center, Beijing, PR China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, PR China.
authors: Pei
authors: P
authors: Yang
authors: Beijing Neurosurgical Institute, Capital Medical University, Beijing, PR China.|Beijing Institute for Brain Disorders, Brain Tumor Center, Beijing, PR China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, PR China.
authors: Zheng
authors: Z
authors: Wang
authors: Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors: Yongping
authors: Y
authors: You
authors: Beijing Neurosurgical Institute, Capital Medical University, Beijing, PR China.|Beijing Institute for Brain Disorders, Brain Tumor Center, Beijing, PR China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, PR China.
authors: Tao
authors: T
authors: Jiang
mesh_terms: D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D044466:Asian People; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002681:China / Q000453:epidemiology; D016000:Cluster Analysis; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D035683:MicroRNAs; D003606:Dacarbazine; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077204:Temozolomide
keywords: IDH1 mutation; glioblastoma; microRNA; temozolomide