Whole‐genome microRNA expression profiling identifies a 5‐microRNA signature as a prognostic biomarker in Chinese patients with primary glioblastoma multiforme

Abstract

BACKGROUND: More reliable clinical outcome prediction is required to better guide more personalized treatment for patients with primary glioblastoma multiforme (GBM). The objective of this study was to identify a microRNA expression signature to improve outcome prediction for patients with primary GBM. METHODS: A cohort of Chinese patients with primary GBM (n = 82) was analyzed using whole‐genome microRNA expression profiling with patients divided into a training set and a testing set. Cox regression and risk‐score analyses were used to develop a 5‐microRNA signature using 41 training samples. The signature was validated in 41 other test samples, in an independent cohort of 35 patients with GBM, and in the Cancer Genome Atlas data set. RESULTS: Patients who had high risk scores according to the 5‐microRNA signature had poor overall survival and progression‐free survival compared with patients who had low risk scores. Multivariate Cox analysis indicated that the 5‐microRNA signature was an independent prognostic biomarker after adjusting for other clinicopathologic and genetic factors, such as extent of resection, temozolomide chemotherapy, preoperative Karnofsky performance status score, isocitrate dehydrogenase 1 (IDH1) mutation, and O‐6‐methylguanine‐DNA methyltransferase (MGMT) promoter methylation status. CONCLUSIONS: The 5‐microRNA signature was identified as an independent risk predictor that identified patients who had a high risk of unfavorable outcome, demonstrating its potential for personalizing cancer management. The authors concluded that this signature should be evaluated in further prospective studies. Cancer 2013. © 2012 American Cancer Society.

Molecular prognostic factors in glioblastoma: state of the art and future challenges

“…These are thought to either inhibit or promote several traits of cancer cells [75]. Another study by Zhang et al performed whole-genome miRNA expression profiling in 82 Chinese GBM patients [76]. The authors identified a five-miRNA signature, comprising of miR-181d, miR-518b, miR-524-5p, miR-566 and miR-1227, that was able to predict patient survival [76].…”

“…Specifically, deregulation of these miRNAs has been detected in GBM, with a wide variety of functional roles in cell proliferation, apoptosis, cell cycle regulation, invasion, angiogenesis and glioma stem cell behavior [66]. Many reports have been published describing the ability of miRNAs to predict GBM patient survival [67][68][69][70][71][72][73][74][75][76][77]. For example, Ben-Hamo and Efroni studied five independent datasets and identified a gene-miRNA network comprising of p38 and its associated miRNA miR-9, which can stratify GBM patients into prognostic subgroups [67].…”

Differential expression of miR200a-3p and miR21 in grade II–III and grade IV gliomas

“…[13][14][15][16][17][18][19] Dysregulation of the expression of microRNAs (miRNAs) is emerging as an important step in early processes during tumorigenesis as well as disease progression/metastasis in various malignancies including GBMs. [20][21][22] The miRNAs function mainly through their ability to bind to the 3′ untranslated regions of mRNAs, leading to their degradation or suppression of their translation. 23 MiRNAs can act as tumor suppressors or oncogenes depending upon the nature of the targeted genes.…”

Epigenetic silencing of KAZALD1 confers a better prognosis and is associated with malignant transformation/progression in glioma

“…Despite recent advances in treatment by a combination of surgery and chemotherapy and/ or radiotherapy, the prognosis of malignant glioma remains extremely poor. Glioblastoma (GBM) is the most common and malignant glioma, and has a median survival time of approximately one year (1)(2)(3)(4)(5)(6)(7). In the United States, 75% of glioma patients die within 5 years of diagnosis (8).…”