Downregulated microRNAs in the differential diagnosis of malignant pleural mesothelioma

Details

• Personal Author:
  Christensen BC ; Gee GV ; Houseman EA ; Ivaldi GP ; Kelsey KT ; Koestler DC ; Marsit CJ ; Resnick MB ; Sugarbaker DJ ; Ugolini D
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Biomarkers Diagnosis Genetics Lung Lung Diseases Microbiology Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety

  More +
• Keywords:
  Author Keywords: Mesothelioma Biostatistics Cancer Diagnostic-techniques Diagnostic-tests Genes Genetic-factors Lung-cancer Lung-cells Lung-disease Lung Adenocarcinoma Malignant-neoplasms Mesothelial-cells MicroRNA Microscopic-analysis Molecular-biology Pathogenesis Pleural-cavity Recombinant-DNA Tumors Wnt Signaling

  More +
• ISSN:
  0020-7136
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; OSHA Region 1 ; OSHA Region 3 ; Pennsylvania ; Rhode Island
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  127
• Issue:
  12
• NIOSHTIC Number:
  nn:20038753
• Citation:
  Int J Cancer 2010 Dec; 127(12):2859-2869
• Contact Point Address:
  Carmen J. Marsit, Department of Pathology and Laboratory Medicine, Brown University, Box G-E537, Providence, RI 02912, USA
• Email:
  carmen_marsit@brown.edu
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4)
• Federal Fiscal Year:
  2011
• NORA Priority Area:
  Construction ; Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20060901
• Source Full Name:
  International Journal of Cancer
• End Date:
  20260831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:679ae28110ecc17f996f5b9f09f58365bd87a74b4da15fa8e5e203d206a6c234127eb01bbbb71dc53bb6a9a0a0c48949301886137d3a561d3d008c9c8f9d2dae
• Download URL:
  https://stacks.cdc.gov/view/cdc/192356/cdc_192356_DS1.pdf
• File Type:
  [PDF - 400.96 KB ]