Microrna-based methods and compositions for the diagnosis, prognosis and treatment of lung cancer
Inventors
Croce, Carlo M. • Yanaihara, Nozomu • Harris, Curtis C.
Assignees
US Department of Health and Human Services • Ohio State University Research Foundation
Publication Number
US-7943318-B2
Publication Date
2011-05-17
Expiration Date
2027-01-03
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Abstract
The present invention provides novel methods and compositions for the diagnosis, prognosis and treatment of lung cancer. The invention also provide methods of identifying anti-lung cancer agents.
Core Innovation
The invention provides novel methods and compositions for the diagnosis, prognosis and treatment of lung cancer based on altered expression levels of specific microRNAs (miRNAs) in lung cancer cells. It encompasses methods of diagnosing whether a subject has, or is at risk for developing, lung cancer by comparing levels of at least one miR gene product in a test sample from the subject to a control sample. Alterations in the miR gene product levels are indicative of the subject having or being at risk for lung cancer.
Further, the invention includes methods of determining the prognosis of a subject with lung cancer by measuring the level of miR gene products associated with adverse prognosis and using that information as an indicator of prognosis. It provides methods of treating lung cancer by administering isolated miR gene products or compounds inhibiting miR expression, depending on whether the miR gene product is down-regulated or up-regulated in lung cancer cells, thereby inhibiting proliferation of cancer cells. The invention also covers pharmaceutical compositions comprising miR gene products or miR expression-inhibition compounds, and methods of identifying anti-lung cancer agents by measuring changes in miR expression following treatment of cells with test agents.
Claims Coverage
The patent includes one independent claim focused on a method for determining the prognosis of a subject with lung cancer by measuring miR gene product levels, with further dependent claims specifying features and uses of this method.
Method of prognosis determination using miR-155 expression level in lung cancer
A method of determining prognosis of a lung cancer subject by measuring at least one miR gene product comprising at least miR-155 in a test sample, where an increase in its level relative to a control sample indicates adverse prognosis.
Use of additional miR gene products for prognosis assessment
Incorporating other miR gene products such as miR-17-3p, miR-106a, miR-93, miR-20, and miR-21 to assess prognosis in lung cancer subjects.
Prognosis determination in lung adenocarcinoma
Applying the prognosis determination method specifically to subjects with lung adenocarcinoma.
Prediction using Kaplan-Meier survival analysis
Using Kaplan-Meier survival curves and associated analyses to predict prognosis based on miR gene expression levels.
Assessment of survival prognosis during therapy and recurrence likelihood
Including ongoing assessment of overall survival prognosis at any therapy point and estimation of lung cancer recurrence likelihood.
Provision of prognosis reports and comparative expression level analysis
Generating reports of prognosis and enabling comparisons of miR gene expression levels against previous samples from the same subject or standard levels.
Use of prognosis to guide treatment and determine disease progression
Utilizing prognosis information to select appropriate treatments, develop treatment strategies, and track disease progression.
Measurement of a second miR gene product with inverse prognosis association
Measuring a second miR gene product such as let-7a-2, let-7b, or miR-145 where a decrease in its level relative to control indicates adverse prognosis.
The claims focus on methods of prognosis determination in lung cancer by measuring miR gene products, particularly miR-155, alone or with additional miRs, and using those levels to predict adverse outcomes, guide treatment, and assess disease progression.
Stated Advantages
Allows detection of lung cancer by identifying miRNA expression alterations in patient samples.
Enables prognosis prediction of lung cancer, including identifying adverse prognosis markers.
Provides therapeutic strategies to inhibit lung cancer cell proliferation by modulating miRNA levels.
Permits identification of anti-lung cancer agents through modulation of miRNA expression profiles.
Documented Applications
Diagnosis of lung cancer by measuring expression levels of specific miRNAs in patient tissue or blood samples.
Prognosis determination of lung cancer patients, including lung adenocarcinoma, based on expression levels of miR-155 and related microRNAs.
Treatment of lung cancer through administration of isolated miR gene products or miR expression-inhibition compounds to regulate cancer cell proliferation.
Use of pharmaceutical compositions containing miR gene products or expression inhibitors for lung cancer therapy.
Screening and identification of anti-lung cancer agents by assessing their impact on miRNA expression in lung cancer cells.
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