Originally published as JCO Early Release 10.1200/JCO.2008.19.4134 on March 9 2009

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Diagnostic Assay Based on hsa-miR-205 Expression Distinguishes Squamous From Nonsquamous Non–Small-Cell Lung Carcinoma

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, Mahesh Mansukhani

From Rosetta Genomics Ltd, Rehovot; Cancer Research Center, Sheba Medical Center, Tel-Hashomer; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Rosetta Genomics Inc, Jersey City, NJ; Departments of Cardiothoracic Surgery and Pathology, New York University School of Medicine; and the Molecular Pathology Laboratory, Columbia University Medical Center, New York, NY.

Corresponding author: Ranit Aharonov, PhD, Rosetta Genomics Ltd, 10 Plaut St, Rehovot 76706, Israel; e-mail: ranit_ah{at}rosettagenomics.com.

Purpose Recent advances in treatment of lung cancer require greater accuracy in the subclassification of non–small-cell lung cancer (NSCLC). Targeted therapies which inhibit tumor angiogenesis pose higher risk for adverse response in cases of squamous cell carcinoma. Interobserver variability and the lack of specific, standardized assays limit the current abilities to adequately stratify patients for such treatments. In this study, we set out to identify specific microRNA biomarkers for the identification of squamous cell carcinoma, and to use such markers for the development of a standardized assay.

Patients and Methods High-throughput microarray was used to measure microRNA expression levels in 122 adenocarcinoma and squamous NSCLC samples. A quantitative real-time polymerase chain reaction (qRT-PCR) platform was used to verify findings in an independent set of 20 NSCLC formalin-fixed, paraffin-embedded (FFPE) samples, and to develop a diagnostic assay using an additional set of 27 NSCLC FFPE samples. The assay was validated using an independent blinded cohort consisting of 79 NSCLC FFPE samples.

Results We identified hsa-miR-205 as a highly specific marker for squamous cell lung carcinoma. A microRNA-based qRT-PCR assay that measures expression of hsa-miR-205 reached sensitivity of 96% and specificity of 90% in the identification of squamous cell lung carcinomas in an independent blinded validation set.

Conclusion Hsa-miR-205 is a highly accurate marker for lung cancer of squamous histology. The standardized diagnostic assay presented here can 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 Recanati foundation, Tel Aviv University (S.I.) and the Flight Attendants Medical Research Institute (FAMRI). G.R. holds the Djerassi Chair in Oncology at the Sackler Faculty of Medicine, Tel Aviv University, Israel.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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