Molecular-based method of cancer diagnosis and prognosis
Inventors
Assignees
US Department of Health and Human Services
Publication Number
US-9181589-B2
Publication Date
2015-11-10
Expiration Date
2030-02-12
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
A gene profiling signature for diagnosis and prognosis of cancer patients is disclosed herein. In one embodiment, the gene signature includes 32 or 79 cancer survival factor-associated genes. Thus, provided herein is a method of determining the prognosis of a subject with a tumor by detecting expression of five of more cancer survival factor-associated genes in a tumor sample and comparing expression of the five or more cancer survival factor-associated genes in the tumor sample to a control. In some examples, an increase in expression of ABCF1, CORO1C, DPP3, PREB, UBE3A, and PTDSS1 in a tumor sample compared to a control sample indicates poor prognosis. Further provided are arrays including probes or antibodies specific for a plurality of cancer survival factor-associated genes or proteins.
Core Innovation
This disclosure relates to a gene expression signature for diagnosing and determining the prognosis of patients with tumors, particularly breast and lung tumors. The invention provides a method for predicting clinical outcomes by detecting expression of cancer survival factor-associated genes in a tumor sample and comparing this to a control. Specific gene signatures include sets of 32 or 79 genes associated with poor survival in breast cancer and a smaller six-gene signature for breast or lung cancer, consisting of ABCF1, CORO1C, DPP3, PREB, UBE3A, and PTDSS1.
The disclosed signatures are highly predictive of survival outcomes and applicable to multiple tumor types. The six-gene signature is especially noted for being rapid and inexpensive for hospital-based assays, contrasting with existing costly tests. The ability to reliably predict survival, including metastasis-free survival, aids in patient selection for appropriate treatments based on disease progression likelihood.
The problem addressed stems from cancer's high mortality, especially via metastasis, which accounts for over 90% of cancer-related deaths. Traditional methods lack reliable classifiers to stratify patients for therapy or targets for intervention. Existing molecular profiling techniques such as microarray expression analysis improve prognostic accuracy but often involve complex, expensive assays. The present invention overcomes these issues by identifying metastasis-relevant genes through mouse metastasis models and subtracting ambient organ-imposed gene expression changes, resulting in gene signatures that robustly correlate with clinical outcomes.
Claims Coverage
The patent includes two independent claims covering methods of detecting expression of cancer survival factor-associated molecules and methods of prognosis involving specific gene sets and treatment steps.
Method for detecting gene expression using all cancer survival factor-associated molecules in Table 1
A method comprising contacting a tumor sample with probes for all cancer survival factor-associated molecules listed in Table 1, and performing real-time quantitative polymerase chain reaction or microarray analysis to detect gene expression.
Method for prognosis based on expression of at least five selected cancer survival factor-associated molecules
Measuring expression of at least five molecules from ABCF1, CORO1C, PREB, DPP3, UBE3A, and PTDSS1 in a tumor sample; determining prognosis by comparison to a non-tumor control where an at least 1.5-fold up-regulation indicates poor prognosis and no significant change indicates good prognosis; and administering an agent (antisense or antibody) that alters expression or activity of upregulated genes.
The claims cover molecular assays detecting specific cancer survival factor-associated genes in tumor samples for diagnostic and prognostic purposes, emphasizing a defined gene panel and methods that guide treatment with agents targeting overexpressed genes.
Stated Advantages
The gene signatures provide highly predictive information about survival outcomes across multiple tumor types.
The six-gene signature enables rapid and inexpensive hospital-based assays, improving accessibility compared to current expensive extramural tests.
Reliable prediction of survival, including metastasis-free survival, facilitates selection of appropriate patient treatment strategies.
Documented Applications
Determining prognosis of subjects with tumors such as breast and lung tumors, including distinguishing benign from malignant tumors.
Predicting clinical outcomes such as overall survival, relapse-free survival, and metastasis-free survival of cancer patients.
Diagnostic classification of tumors by expression levels of cancer survival factor-associated genes.
Screening subjects to guide administration of therapeutic agents that alter expression or activity of specific cancer survival factor-associated molecules.
Treatment of cancer by administering agents that reduce expression or activity of upregulated cancer survival factor-associated molecules to delay tumor development, reduce metastasis, and increase survival.
Interested in licensing this patent?