Identification of microRNA Biomarkers for Lung Cancer

DESCRIPTION (provided by applicant): In the United States, lung cancer has the highest incidence and the highest mortality rate of all cancers. An estimated 215,020 new cases of lung cancer and an estimated 161,840 deaths from lung cancer will occur in the United States during 2008. This high mortality rate of lung cancer has been attributed in part to the fact that majority (gt75%) of the patients are diagnosed with regional or distant metastasis at first presentation of the disease, and in part to the lack of highly effective therapies. It has been shown that patients diagnosed with early stage I have a better (50%) chance of 5-yr survival than those in later stage IV (lt10%), suggesting the need for early detection. There are currently no approved screening methods for early detection of lung cancer. The long term goal of this project is to develop novel biofluid-based lung cancer diagnostic markers that can be used for non-invasive, affordable detection of lung cancer at an early stage at which medical intervention can benefit the patients. We propose to use our microRNA (miRNA) technologies to identify miRNAs that are differentially expressed between cancer-free subjects and lung cancer patients. We will focus on two subtypes of non small cell lung cancer, adenocarcinoma and squamous cell carcinoma, because these constitute the majority of lung cancer cases. We will use highly annotated clinical samples, provided from our academic collaborators, to assemble age, gender and environment-balanced sample sets to analyze early stage cancers of both subtypes. Our investigations will focus on developing generic miRNA biomarkers or biomarker classifiers for lung cancer, as well as biomarkers that are specific for each gender or cancer subtype. Our phase I goals are to demonstrate feasibility of identifying highly-specific and sensitive lung cancer biomarkers signatures from biofluids. Future investigations will establish the clinical validity of the biomarker signatures, and development of comprehensive assays to test for these signatures. PUBLIC HEALTH RELEVANCE: Lung cancer has the highest incidence mortality rate of all cancers. Patients diagnosed early have a better chance of survival than those in later stages, suggesting the need for early detection, but there are currently no effective lung cancer screening methods. We propose to identify microRNA biomarkers that can be detected in a non invasive sample obtain from patients, and are both sensitive and specific for lung cancer.