MiR-21 Expression in the Tumor Stroma of Oral Squamous Cell Carcinoma: An Independent Biomarker of Disease Free Survival
Open Access
- 22 April 2014
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 9 (4), e95193
- https://doi.org/10.1371/journal.pone.0095193
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.This publication has 30 references indexed in Scilit:
- Pleiotropic actions of miR-21 highlight the critical role of deregulated stromal microRNAs during colorectal cancer progressionCell Death & Disease, 2013
- High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosisTumor Biology, 2013
- Programmed cell death 4 nuclear loss and miR-21 or activated Akt overexpression in esophageal squamous cell carcinogenesisDiseases of the Esophagus, 2011
- Different miRNA signatures of oral and pharyngeal squamous cell carcinomas: a prospective translational studyBritish Journal of Cancer, 2011
- Knockdown of miR-21 in human breast cancer cell lines inhibits proliferation, in vitro migration and in vivotumor growthBreast Cancer Research, 2011
- High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patientsClinical & Experimental Metastasis, 2010
- Fluorescence-Based Codetection with Protein Markers Reveals Distinct Cellular Compartments for Altered MicroRNA Expression in Solid TumorsClinical Cancer Research, 2010
- MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologueCardiovascular Research, 2009
- MicroRNA-21 Targets Sprouty2 and Promotes Cellular OutgrowthsMolecular Biology of the Cell, 2008
- Fibroblasts in cancerNature Reviews Cancer, 2006