Diagnostic Assay Based on hsa-miR-205 Expression Distinguishes Squamous From Nonsquamous Non–Small-Cell Lung Carcinoma
(2009)
Journal - Journal of Clinical Oncology
Abstract :
Danit Lebanony,
Hila Benjamin,
Shlomit Gilad,
Meital Ezagouri,
Avital Dov,
Karin Ashkenazi,
Nir Gefen,
Shai Izraeli,
Gideon Rechavi,
Harvey Pass,
Daisuke Nonaka,
Junjie Li,
Yael Spector,
Nitzan Rosenfeld,
Ayelet Chajut,
Dalia Cohen,
Ranit Aharonov and
Mahesh Mansukhani
Purpose: Recent advances in treatment of lung cancer require greateraccuracy in the subclassification of non–small-cell lungcancer (NSCLC). Targeted therapies which inhibit tumor angiogenesispose higher risk for adverse response in cases of squamous cellcarcinoma. Interobserver variability and the lack of specific,standardized assays limit the current abilities to adequatelystratify patients for such treatments. In this study, we setout to identify specific microRNA biomarkers for the identificationof squamous cell carcinoma, and to use such markers for thedevelopment of a standardized assay.
Patients and Methods: High-throughput microarray was used to measure microRNA expressionlevels in 122 adenocarcinoma and squamous NSCLC samples. A quantitativereal-time polymerase chain reaction (qRT-PCR) platform was usedto verify findings in an independent set of 20 NSCLC formalin-fixed,paraffin-embedded (FFPE) samples, and to develop a diagnosticassay using an additional set of 27 NSCLC FFPE samples. Theassay was validated using an independent blinded cohort consistingof 79 NSCLC FFPE samples.
Results: We identified hsa-miR-205 as a highly specific marker for squamouscell lung carcinoma. A microRNA-based qRT-PCR assay that measuresexpression of hsa-miR-205 reached sensitivity of 96% and specificityof 90% in the identification of squamous cell lung carcinomasin an independent blinded validation set.
Conclusion: Hsa-miR-205 is a highly accurate marker for lung cancer of squamoushistology. The standardized diagnostic assay presented herecan provide highly accurate subclassification of NSCLC patients.
D.L., H.B., and S.G. contributed equally to this work.
Supported by the Israeli Cancer Association and the Recanatifoundation, Tel Aviv University (S.I.) and the Flight AttendantsMedical Research Institute (FAMRI). G.R. holds the DjerassiChair in Oncology at the Sackler Faculty of Medicine, Tel AvivUniversity, Israel.
Authors' disclosures of potential conflicts of interest andauthor contributions are found at the end of this article.