title: MiR-21 expression in the tumor stroma of oral squamous cell carcinoma: an independent biomarker of disease free survival.
abstract: Oral squamous cell carcinoma (OSCC) patients have a high mortality rate; thus, new clinical biomarkers and therapeutic options are needed. MicroRNAs (miRNAs) are short noncoding RNAs that regulate posttranscriptional gene expression and are commonly deregulated in OSCC and other cancers. MicroRNA-21 (miR-21) is the most consistently overexpressed miRNA in several types of cancer, and it might be a useful clinical biomarker and therapeutic target. To better understand the role of miR-21 in OSCC, paraffin-embedded tumor tissue samples from 86 patients with primary OSCC were analyzed by in situ hybridization. We found that miR-21 was primarily expressed in the tumor stroma and in some tumor-associated blood vessels with no expression in the adjacent normal epithelia or stroma. Using image analysis, we quantitatively estimated miR-21 expression levels specifically in the stroma of a cohort of OSCC samples. These miR-21 levels significantly correlated with disease free survival with the highest levels being located in the stroma. Stromal miR-21 expression was independently associated with a poorer prognosis, even after adjusting for clinical parameters (perineural invasion and N-stage) in a multivariate analysis. In summary, we have shown that miR-21 is located in the carcinoma cells, stroma and blood vessels of tumors, and its expression specifically in the stromal compartment has a negative prognostic value in OSCC.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Nora
authors.initials: N
authors.lastname: Hedbäck
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: David H
authors.initials: DH
authors.lastname: Jensen
authors.affiliation: Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lena
authors.initials: L
authors.lastname: Specht
authors.affiliation: Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anne-Marie K
authors.initials: AM
authors.lastname: Fiehn
authors.affiliation: Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Marianne H
authors.initials: MH
authors.lastname: Therkildsen
authors.affiliation: Centre for Genomic Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lennart
authors.initials: L
authors.lastname: Friis-Hansen
authors.affiliation: Department of Oral Health Sciences, Faculty of Health Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Erik
authors.initials: E
authors.lastname: Dabelsteen
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: von Buchwald
mesh_terms: D061354:Acinar Cells / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D015999:Multivariate Analysis; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D018709:Statistics, Nonparametric; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C524940:MIRN21 microRNA, human; D035683:MicroRNAs
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