A diagnostic assay based on microRNA expression accurately identifies malignant pleural mesothelioma.
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.
Benjamin
Hila
H
Rosetta Genomics Ltd., 10 Plaut St., Rehovot 76706, Israel.
Lebanony
Danit
D
Rosenwald
Shai
S
Cohen
Lahav
L
Gibori
Hadas
H
Barabash
Naama
N
Ashkenazi
Karin
K
Goren
Eran
E
Meiri
Eti
E
Morgenstern
Sara
S
Perelman
Marina
M
Barshack
Iris
I
Goren
Yaron
Y
Edmonston
Tina Bocker
TB
Chajut
Ayelet
A
Aharonov
Ranit
R
Bentwich
Zvi
Z
Rosenfeld
Nitzan
N
Cohen
Dalia
D
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
D014408:Biomarkers, Tumor; D035683:MicroRNAs