title: A diagnostic assay based on microRNA expression accurately identifies malignant pleural mesothelioma.
abstract: The definitive identification of malignant pleural mesothelioma (MPM) has significant clinical implications, yet other malignancies often involve the lung pleura, confounding the diagnosis of MPM. In the absence of accurate markers, MPM can be difficult to distinguish from peripheral lung adenocarcinoma and metastatic epithelial cancers. MicroRNA expression is tissue-specific and highly informative for identifying tumor origin. We identified microRNA biomarkers for the differential diagnosis of MPM and developed a standardized microRNA-based assay. Formalin-fixed, paraffin-embedded samples of 33 MPM and 210 carcinomas were used for assay development. Using microarrays, we identified microRNAs differentially expressed between MPM and various carcinomas. Hsa-miR-193-3p was overexpressed in MPM, while hsa-miR-200c and hsa-miR-192 were overexpressed in peripheral lung adenocarcinoma and carcinomas that frequently metastasize to lung pleura. We developed a standardized diagnostic assay based on the expression of these microRNAs. The assay reached a sensitivity of 100% and a specificity of 94% in a blinded validation set of 68 samples from the lung and pleura. This diagnostic assay can provide a useful tool in the differential diagnosis of MPM from other malignancies in the pleura.
authors.affiliation: Rosetta Genomics Ltd., 10 Plaut St., Rehovot 76706, Israel.
authors.forename: Hila
authors.initials: H
authors.lastname: Benjamin
authors.forename: Danit
authors.initials: D
authors.lastname: Lebanony
authors.forename: Shai
authors.initials: S
authors.lastname: Rosenwald
authors.forename: Lahav
authors.initials: L
authors.lastname: Cohen
authors.forename: Hadas
authors.initials: H
authors.lastname: Gibori
authors.forename: Naama
authors.initials: N
authors.lastname: Barabash
authors.forename: Karin
authors.initials: K
authors.lastname: Ashkenazi
authors.forename: Eran
authors.initials: E
authors.lastname: Goren
authors.forename: Eti
authors.initials: E
authors.lastname: Meiri
authors.forename: Sara
authors.initials: S
authors.lastname: Morgenstern
authors.forename: Marina
authors.initials: M
authors.lastname: Perelman
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.forename: Yaron
authors.initials: Y
authors.lastname: Goren
authors.forename: Tina Bocker
authors.initials: TB
authors.lastname: Edmonston
authors.forename: Ayelet
authors.initials: A
authors.lastname: Chajut
authors.forename: Ranit
authors.initials: R
authors.lastname: Aharonov
authors.forename: Zvi
authors.initials: Z
authors.lastname: Bentwich
authors.forename: Nitzan
authors.initials: N
authors.lastname: Rosenfeld
authors.forename: Dalia
authors.initials: D
authors.lastname: Cohen
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008654:Mesothelioma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D046228:Microarray Analysis / Q000379:methods* / Q000592:standards; D010997:Pleural Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs