We have shown genetic alterations and microRNA dysregulation in hematopoietic and solid tumors, including lung cancer, the major cause of cancer death in the USA. Recently, we explored microRNA expression profiles in lung tumors, normal lung tissues and plasma samples from cases with variable prognosis involved in a completed spiral CT screening trial with extensive follow up. The trial involved 1025 individuals age 50 years or older, who smoked at least a pack of cigarettes a day for 20 years or more. Profiling of plasma samples collected 1-2 years before the onset of disease, at the time of CT detection, and in disease-free smokers enrolled in the screening trial, provided microRNA expression signatures with strong predictive, diagnostic and prognostic potential (Boeri M. et al. "microRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer", Proc. Nat. Acad. Sci. USA, 108:3712-3718, March 1, 2011). These signatures were validated in an independent cohort from a second randomized spiral - CT trial. These results indicate a role of microRNAs as molecular predictors of lung cancer development and aggressiveness and have important clinical implications for lung cancer management. We propose to validate these signatures by using NanoString technology and deep sequencing of microRNAs by taking advantage of large cohorts of patients at NYU (Dr. H. Pass) and at the National Cancer Institute of Italy, Milan, (Drs. U. Pastorino and G. Sozzi). In addition, we propose to investigate the dysregulation of larger non-coding RNAs in the tumors, normal tissues and plasma in the same cohorts of patients, since it could provide novel powerful biomarkers for the early detection and prevention of lung cancer.

Public Health Relevance

Lung cancer is the first cause of cancer death in the USA and is, for the most part, incurable. We propose to develop reliable and powerful biomarkers capable to detect malignant disease long before lung cancer is clinically detectable by using a non-invasive approach exploiting microRNA and lncRNA dysregulation in plasma of individuals at risk.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01CA166905-01A1
Application #
8504396
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Wang, Wendy
Project Start
2013-07-02
Project End
2018-06-30
Budget Start
2013-07-02
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$967,089
Indirect Cost
$159,052
Name
Ohio State University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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Laganà, Alessandro; Acunzo, Mario; Romano, Giulia et al. (2014) miR-Synth: a computational resource for the design of multi-site multi-target synthetic miRNAs. Nucleic Acids Res 42:5416-25
He, Wei A; Calore, Federica; Londhe, Priya et al. (2014) Microvesicles containing miRNAs promote muscle cell death in cancer cachexia via TLR7. Proc Natl Acad Sci U S A 111:4525-9
Sozzi, Gabriella; Boeri, Mattia; Rossi, Marta et al. (2014) Clinical utility of a plasma-based miRNA signature classifier within computed tomography lung cancer screening: a correlative MILD trial study. J Clin Oncol 32:768-73