Yan Wei, Liu Yanwei, Yang Pei, Wang Zheng, You Yongping, Jiang Tao
Beijing Neurosurgical Institute, Capital Medical University, Beijing, PR China.
Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
Oncotarget. 2015 May 10;6(13):11676-82. doi: 10.18632/oncotarget.3258.
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.
越来越多的证据表明，基于客观基因改变来定义分子亚型可能允许针对各种癌症采用更合理、针对患者的分子靶向治疗方法。本研究的目的是基于中国人群中的微小RNA（miRNA）谱对原发性胶质母细胞瘤（pGBM）进行亚型分类。在此，分析了82个pGBM样本的miRNA表达谱，并使用78个独立的pGBM样本进行qRT-PCR验证。我们发现中国pGBM样本中存在两个具有不同预后和对替莫唑胺（TMZ）化疗敏感性的不同亚组。一种亚型是TMZ化疗耐药型（称为TCR亚型），预后较差。另一种亚型是TMZ化疗敏感型（称为TCS亚型），与TCR亚型相比预后相对较好。然后鉴定出一个由7个miRNA组成的分类器（miR-1280、miR-1238、miR-938和miR-423-5p（在TCR亚型中过表达）；以及let-7i、miR-151-3p和miR-93（在TCR亚型中下调）），可用于将pGBM样本分配到相应亚型。该分类器使用内部和外部样本进行了验证。同时，还分析了TCR和TCS亚型的基因改变。TCR亚型的特征是无IDH1突变，以及EGFR和Ki-67过表达。TCS亚型则呈现相反的情况。综上所述，结果表明存在一个预后较差且对TMZ化疗耐药的不同亚组。
