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Downregulated microRNAs in the differential diagnosis of malignant pleural mesothelioma.

Authors
Gee-GV; Koestler-DC; Christensen-BC; Sugarbaker-DJ; Ugolini-D; Ivaldi-GP; Resnick-MB; Houseman-EA; Kelsey-KT; Marsit-CJ
Source
Int J Cancer 2010 Dec; 127(12):2859-2869
NIOSHTIC No.
20038753
Abstract
Malignant pleural mesothelioma (MPM) is a rapidly fatal disease whose diagnosis, particularly through less invasive techniques such as analysis of pleural effusion, can be challenging. Currently, a commercially available diagnostic test based on microRNA (miRNA) expression patterns is purported to distinguish between mesothelioma and lung adenocarcinoma. Yet, the biological basis of this technology has not been reported in the literature, and little research has been aimed at determining how differential miRNA expression contributes to the differences in pathogenesis between these diseases, both of which can be caused by asbestos exposure. We sought to illuminate the molecular differences between mesothelioma and lung adenocarcinoma by using miRNA microarrays to identify patterns in the most differentially expressed miRNAs. From this, we identified a panel of miRNAs, including members of the miR-200 gene family, that were all downregulated in MPM compared to lung adenocarcinoma. Using the more sensitive detection method of quantitative RT-PCR on an independent series of tumors, we validated the specificity of these alterations in 100 MPMs and 32 lung adenocarcinomas. Statistical analysis reveals that these miRNAs exceed the current recommendations for biomarkers and could greatly aid in the differential diagnosis. Further examination led us to predict that they act as redundant regulators of wnt signaling and suggests a role for this pathway in tumor progression. This research points to novel approaches using miRNAs whose decreased expression is unique to mesothelioma as potentially suitable for rapid diagnosis and reveals prospective new targets for the treatment of this deadly disease.
Keywords
Cancer; Mesothelial-cells; Recombinant-DNA; Genes; Lung-cancer; Lung-cells; Neoplasms; Pleural-cavity; Tumors; Diagnostic-techniques; Malignant-neoplasms; Microscopic-analysis; Diagnostic-tests; Pathogenesis; Genetic-factors; Molecular-biology; Lung-disease; Biomarkers; Biostatistics; Author Keywords: mesothelioma; microRNA; wnt signaling; lung adenocarcinoma
Contact
Carmen J. Marsit, Department of Pathology and Laboratory Medicine, Brown University, Box G-E537, Providence, RI 02912, USA
CODEN
IJCNAW
CAS No.
1332-21-4
Publication Date
20101215
Document Type
Journal Article
Email Address
carmen_marsit@brown.edu
Funding Type
Cooperative Agreement
Fiscal Year
2011
NTIS Accession No.
NTIS Price
Identifying No.
Cooperative-Agreement-Number-U24-OH-009077
Issue of Publication
12
ISSN
0020-7136
Source Name
International Journal of Cancer
State
RI; MA; PA
Performing Organization
University of Pittsburgh at Pittsburgh
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