Prognostic Value of microRNA-221/2 and 17-92 Families in Primary Glioblastoma Patients Treated with Postoperative Radiotherapy

International Journal of Molecular Sciences

Wolfgang Wick¹  Christine Jungk²  Benito Campos²  Christel Herold-Mende²  Rolf Warta²  Andreas Unterberg²  Elena Schnabel³  Amir Abdollahi³  Andreas Mock³  Jürgen Debus³  Maximilian Knoll³  Christian Schwager³  Laila König³ 

[1] Department of Neuro-Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany;Division of Experimental Neurosurgery, Department of Neurosurgery, Heidelberg University Hospital, 69120 Heidelberg, Germany;German Cancer Consortium (DKTK) Core-Center, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany;

关键词: glioblastoma;    radiochemotherapy;    microRNA;    miR-221;    miR-222;    miR-17-92;   

DOI  :  10.3390/ijms22062960

来源: DOAJ

【 摘 要 】

MicroRNAs (miRs) are non-coding master regulators of transcriptome that could act as tumor suppressors (TSs) or oncogenes (oncomiRs). We aimed to systematically investigate the relevance of miRs as prognostic biomarkers in primary glioblastoma multiforme (GBM) treated with postoperative radio(chemo)therapy (PORT). For hypothesis generation, tumor miR expression by Agilent 8x15K human microRNA microarrays and survival data from 482 GBM patients of The Cancer Genome Atlas (TCGA cohort) were analyzed using Cox-PH models. Expression of candidate miRs with prognostic relevance (miR-221/222; miR-17-5p, miR-18a, miR-19b) was validated by qRT-PCR using Taqman technology on an independent validation cohort of GBM patients (n = 109) treated at Heidelberg University Hospital (HD cohort). In TCGA, 50 miRs showed significant association with survival. Among the top ranked prognostic miRs were members of the two miR families miR-221/222 and miR-17-92. Loss of miR-221/222 was correlated with improved prognosis in both cohorts (TCGA, HD) and was an independent prognostic marker in a multivariate analysis considering demographic characteristics (age, sex, Karnofsky performance index (KPI)), molecular markers (O-6-methylguanine-DNA methyltransferase (MGMT) methylation, IDH mutation status) and PORT as co-variables. The prognostic value of miR-17-92 family members was ambiguous and in part contradictory by direct comparison of the two cohorts, thus warranting further validation in larger prospective trials.

【 授权许可】

Unknown