PMID- 33803955
OWN - NLM
STAT- MEDLINE
DCOM- 20210430
LR  - 20210430
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 6
DP  - 2021 Mar 15
TI  - Prognostic Value of microRNA-221/2 and 17-92 Families in Primary Glioblastoma 
      Patients Treated with Postoperative Radiotherapy.
LID - 10.3390/ijms22062960 [doi]
LID - 2960
AB  - 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.
FAU - Schnabel, Elena
AU  - Schnabel E
AD  - German Cancer Consortium (DKTK) Core-Center, German Cancer Research Center 
      (DKFZ), 69120 Heidelberg, Germany.
AD  - Heidelberg Ion-Beam Therapy Center (HIT), Divisions of Molecular & Translational 
      Radiation Oncology, Heidelberg University Hospital (UKHD), 69120 Heidelberg, 
      Germany.
AD  - National Center for Radiation Research in Oncology (NCRO), Heidelberg Institute 
      of Radiation Oncology (HIRO), DKFZ and UKHD, 69120 Heidelberg, Germany.
AD  - CCU Translational Radiation Oncology, National Center for Tumor Diseases (NCT), 
      DKFZ and UKHD, 69120 Heidelberg, Germany.
AD  - Center for Child and Adolescent Medicine, General Pediatrics, Heidelberg 
      University Hospital, 69120 Heidelberg, Germany.
FAU - Knoll, Maximilian
AU  - Knoll M
AUID- ORCID: 0000-0002-9037-3980
AD  - German Cancer Consortium (DKTK) Core-Center, German Cancer Research Center 
      (DKFZ), 69120 Heidelberg, Germany.
AD  - Heidelberg Ion-Beam Therapy Center (HIT), Divisions of Molecular & Translational 
      Radiation Oncology, Heidelberg University Hospital (UKHD), 69120 Heidelberg, 
      Germany.
AD  - National Center for Radiation Research in Oncology (NCRO), Heidelberg Institute 
      of Radiation Oncology (HIRO), DKFZ and UKHD, 69120 Heidelberg, Germany.
AD  - CCU Translational Radiation Oncology, National Center for Tumor Diseases (NCT), 
      DKFZ and UKHD, 69120 Heidelberg, Germany.
FAU - Schwager, Christian
AU  - Schwager C
AD  - German Cancer Consortium (DKTK) Core-Center, German Cancer Research Center 
      (DKFZ), 69120 Heidelberg, Germany.
AD  - Heidelberg Ion-Beam Therapy Center (HIT), Divisions of Molecular & Translational 
      Radiation Oncology, Heidelberg University Hospital (UKHD), 69120 Heidelberg, 
      Germany.
AD  - National Center for Radiation Research in Oncology (NCRO), Heidelberg Institute 
      of Radiation Oncology (HIRO), DKFZ and UKHD, 69120 Heidelberg, Germany.
AD  - CCU Translational Radiation Oncology, National Center for Tumor Diseases (NCT), 
      DKFZ and UKHD, 69120 Heidelberg, Germany.
FAU - Warta, Rolf
AU  - Warta R
AUID- ORCID: 0000-0003-2821-4361
AD  - Division of Experimental Neurosurgery, Department of Neurosurgery, Heidelberg 
      University Hospital, 69120 Heidelberg, Germany.
FAU - Mock, Andreas
AU  - Mock A
AD  - German Cancer Consortium (DKTK) Core-Center, German Cancer Research Center 
      (DKFZ), 69120 Heidelberg, Germany.
AD  - Division of Experimental Neurosurgery, Department of Neurosurgery, Heidelberg 
      University Hospital, 69120 Heidelberg, Germany.
AD  - National Center for Tumor Diseases (NCT) Heidelberg, Department of Medical 
      Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
AD  - National Center for Tumor Diseases (NCT) Heidelberg, Department of Translational 
      Medical Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, 
      Germany.
FAU - Campos, Benito
AU  - Campos B
AD  - Division of Experimental Neurosurgery, Department of Neurosurgery, Heidelberg 
      University Hospital, 69120 Heidelberg, Germany.
FAU - Konig, Laila
AU  - Konig L
AD  - German Cancer Consortium (DKTK) Core-Center, German Cancer Research Center 
      (DKFZ), 69120 Heidelberg, Germany.
AD  - Heidelberg Ion-Beam Therapy Center (HIT), Divisions of Molecular & Translational 
      Radiation Oncology, Heidelberg University Hospital (UKHD), 69120 Heidelberg, 
      Germany.
AD  - National Center for Radiation Research in Oncology (NCRO), Heidelberg Institute 
      of Radiation Oncology (HIRO), DKFZ and UKHD, 69120 Heidelberg, Germany.
AD  - CCU Translational Radiation Oncology, National Center for Tumor Diseases (NCT), 
      DKFZ and UKHD, 69120 Heidelberg, Germany.
FAU - Jungk, Christine
AU  - Jungk C
AD  - Division of Experimental Neurosurgery, Department of Neurosurgery, Heidelberg 
      University Hospital, 69120 Heidelberg, Germany.
FAU - Wick, Wolfgang
AU  - Wick W
AD  - Department of Neuro-Oncology, Heidelberg University Hospital, 69120 Heidelberg, 
      Germany.
FAU - Unterberg, Andreas
AU  - Unterberg A
AD  - Division of Experimental Neurosurgery, Department of Neurosurgery, Heidelberg 
      University Hospital, 69120 Heidelberg, Germany.
FAU - Debus, Jurgen
AU  - Debus J
AD  - German Cancer Consortium (DKTK) Core-Center, German Cancer Research Center 
      (DKFZ), 69120 Heidelberg, Germany.
AD  - Heidelberg Ion-Beam Therapy Center (HIT), Divisions of Molecular & Translational 
      Radiation Oncology, Heidelberg University Hospital (UKHD), 69120 Heidelberg, 
      Germany.
AD  - National Center for Radiation Research in Oncology (NCRO), Heidelberg Institute 
      of Radiation Oncology (HIRO), DKFZ and UKHD, 69120 Heidelberg, Germany.
AD  - CCU Translational Radiation Oncology, National Center for Tumor Diseases (NCT), 
      DKFZ and UKHD, 69120 Heidelberg, Germany.
FAU - Herold-Mende, Christel
AU  - Herold-Mende C
AUID- ORCID: 0000-0002-1915-745X
AD  - Division of Experimental Neurosurgery, Department of Neurosurgery, Heidelberg 
      University Hospital, 69120 Heidelberg, Germany.
FAU - Abdollahi, Amir
AU  - Abdollahi A
AUID- ORCID: 0000-0002-8016-5897
AD  - German Cancer Consortium (DKTK) Core-Center, German Cancer Research Center 
      (DKFZ), 69120 Heidelberg, Germany.
AD  - Heidelberg Ion-Beam Therapy Center (HIT), Divisions of Molecular & Translational 
      Radiation Oncology, Heidelberg University Hospital (UKHD), 69120 Heidelberg, 
      Germany.
AD  - National Center for Radiation Research in Oncology (NCRO), Heidelberg Institute 
      of Radiation Oncology (HIRO), DKFZ and UKHD, 69120 Heidelberg, Germany.
AD  - CCU Translational Radiation Oncology, National Center for Tumor Diseases (NCT), 
      DKFZ and UKHD, 69120 Heidelberg, Germany.
LA  - eng
GR  - DFG, SFB 1389, Unite, Project-ID 404521405/German Research Foundation 
      Collaborative Research Center/
GR  - (NCT-PRO)/intramural funds of the National Center for Tumor Diseases/
GR  - n/a/Heinrich F.C. Behr stipend/
PT  - Journal Article
DEP - 20210315
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (MIR17HG, human)
RN  - 0 (MIRN17 microRNA, human)
RN  - 0 (MIRN18A microRNA, human)
RN  - 0 (MIRN19 microRNA, human)
RN  - 0 (MIRN221 microRNA, human)
RN  - 0 (MIRN222 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Long Noncoding)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/genetics
MH  - Disease-Free Survival
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Glioblastoma/genetics/pathology/*radiotherapy/surgery
MH  - Humans
MH  - Male
MH  - MicroRNAs/*genetics
MH  - Middle Aged
MH  - Prognosis
MH  - Promoter Regions, Genetic/genetics
MH  - RNA, Long Noncoding/*genetics
MH  - Tissue Array Analysis
MH  - Transcriptome/genetics
PMC - PMC7998975
OTO - NOTNLM
OT  - glioblastoma
OT  - miR-17-92
OT  - miR-221
OT  - miR-222
OT  - microRNA
OT  - prognosis
OT  - radiochemotherapy
COIS- The authors declare that they have no competing interest.
EDAT- 2021/04/04 06:00
MHDA- 2021/05/01 06:00
PMCR- 2021/03/15
CRDT- 2021/04/03 01:16
PHST- 2021/02/19 00:00 [received]
PHST- 2021/03/08 00:00 [revised]
PHST- 2021/03/08 00:00 [accepted]
PHST- 2021/04/03 01:16 [entrez]
PHST- 2021/04/04 06:00 [pubmed]
PHST- 2021/05/01 06:00 [medline]
PHST- 2021/03/15 00:00 [pmc-release]
AID - ijms22062960 [pii]
AID - ijms-22-02960 [pii]
AID - 10.3390/ijms22062960 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Mar 15;22(6):2960. doi: 10.3390/ijms22062960.