title: MiR-21 expression in the tumor cell compartment holds unfavorable prognostic value in gliomas.
abstract: High-grade gliomas are some of the most lethal forms of human cancer, and new clinical biomarkers and therapeutic targets are highly needed. MicroRNAs (miRNAs), a group of short noncoding RNAs, hold great potential as new biomarkers and targets as they are commonly deregulated in a variety of diseases including gliomas. MicroRNA-21 (miR-21) is the most consistently overexpressed miRNA in several cancers including gliomas and is therefore very promising as a useful clinical biomarker and therapeutic target. To better understand the role of miR-21 in gliomas, paraffin-embedded glioma tissue samples from 193 patients with grade I, II, III, and IV tumors were analyzed by in situ hybridization (ISH) using LNA-DNA chimeric probes. We found miR-21 expression in tumor cells and tumor-associated blood vessels, whereas no expression was seen in adjacent normal brain parenchyma. Using advanced image analysis we obtained quantitative estimates reflecting the miR-21 expression levels in each of these compartments. The miR-21 levels correlated significantly with grade [p = 0.027, r                 (s) = 0.161, 95 % confidence interval (CI), 0.015-0.301] with the highest levels measured in glioblastomas. Only tumor cell miR-21 was associated with poor prognosis when adjusting for known clinical parameters (age, grade, and sex) in a multivariate analysis [p = 0.049, hazard ratio (HR) = 1.545, 95 % CI, 1.002-2.381]. In conclusion, we have shown that miR-21 is located in both tumor cells and tumor blood vessels and that its level in the tumor cell compartment holds unfavorable prognostic value in gliomas.
authors.affiliation: Department of Pathology, Odense University Hospital, Winsløwparken, 15, 3. Floor, 5000, Odense C, Denmark. simon.hermansen@ouh.regionsyddanmark.dk
authors.forename: Simon Kjær
authors.initials: SK
authors.lastname: Hermansen
authors.forename: Rikke Hedegaard
authors.initials: RH
authors.lastname: Dahlrot
authors.forename: Boye Schnack
authors.initials: BS
authors.lastname: Nielsen
authors.forename: Steinbjørn
authors.initials: S
authors.lastname: Hansen
authors.forename: Bjarne Winther
authors.initials: BW
authors.lastname: Kristensen
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015342:DNA Probes; D005260:Female; D020869:Gene Expression Profiling; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides / Q000737:chemistry; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D015342:DNA Probes; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D009841:Oligonucleotides; C477371:locked nucleic acid