MicroRNA-based Assay for Differential Diagnosis of Mesothelioma
H Benjamin, D Lebanony, K Ashkenazi, S Tabak, I Leizerman, D Nonaka, S Morgenstern, Z Bentwich, S Rosenwald, A Chajut, D Cohen. Rosetta Genomics, Rehovot, Israel; NYU School of Medicine, New York, NY; Rabin Medical Center Belinson Campus, Petach Tikva, Israel
Background: Malignant mesothelioma is an aggressive pleural neoplasm, strongly linked to environmental exposure, particularly asbestos exposure. Mesothelioma in the lung pleura is difficult to differentiate from other tumors in the lung pleura, such as primary lung adenocarcinoma protruding into the pleural space and metastatic adenocarcinoma from other tissues in the same environment. Here we addressed the increasing need for accurate differential diagnosis of these tumors using expression profiles of microRNAs, a family of small, non-coding RNAs whose tissue-specificity has a proven applicability for the identification of cancer tissue type and histology.
Design: RNA was extracted from dozens of FFPE samples of mesothelioma, lung adenocarcinoma, and additional tumor types, using proprietary protocols that preserve the small RNA fraction. Initial profiling using microRNA microarrays identified potential microRNA biomarkers that can be used to differentiate mesothelioma from other tumors and tumor types. A qRT-PCR assay was developed that utilizes the microRNA markers for this differential diagnosis, and was validated using an independent blinded validation set.
Results: A small set of microRNA biomarkers was identified, that is strongly differentially expressed between mesothelioma, lung adenocarcinoma, and other confounding tumor types. A diagnostic qRT-PCR assay based on the expression level of the specific microRNAs in FFPE samples exceeded 90% accuracy in the differential diagnosis of mesothelioma on blinded validation samples.
Conclusions: MicroRNAs are highly efficient biomarkers for cancer diagnosis. A robust and simple assay based on the expression level of a few microRNA biomarkers can accurately differentiate mesothelioma from other possible tumors in the lung pleura.
Tuesday, March 10, 2009 11:15 AM
Platform Session: Section F 2, Tuesday Morning