Molecular-based method of cancer diagnosis and prognosis
Inventors
Assignees
US Department of Health and Human Services
Publication Number
US-8715928-B2
Publication Date
2014-05-06
Expiration Date
2030-02-12
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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. Also provided is a method of treating a patient diagnosed with cancer by administering a therapeutically effective amount of an agent that alters expression or activity of one or more of the disclosed cancer survival factor-associated genes. Further provided are arrays including probes or antibodies specific for a plurality of cancer survival factor-associated genes or proteins.
Core Innovation
The invention discloses gene profiling signatures for diagnosing and prognosing cancer patients by detecting expression of multiple cancer survival factor-associated genes in tumor samples. These gene signatures include sets of 32 or 79 genes, as well as a specific set of six genes (ABCF1, CORO1C, DPP3, PREB, UBE3A, and PTDSS1), whose altered expression correlates with poor survival outcomes in subjects with tumors such as breast and lung cancer. Methods involve detecting expression of at least five such cancer survival factor-associated genes and comparing them to controls to predict prognosis, including distinguishing between benign and malignant tumors.
The problem addressed relates to the need for reliable prognostic and diagnostic classifiers to stratify tumor subjects for therapy and identify therapeutic targets, especially due to metastatic disease causing more than 90% of cancer deaths. Current gene expression-based assays have utility but can be costly and limited. This invention solves these issues by identifying metastasis gene signatures that reliably predict survival outcomes and progression, applicable to multiple tumor types, and enabling rapid, inexpensive hospital-based assays.
Claims Coverage
The patent contains multiple independent claims covering methods of detecting gene expression of specific cancer survival factor-associated molecules in lung and breast tumors.
Detection of six specific cancer survival factor-associated molecules in tumor samples
The method involves detecting expression of six cancer survival factor-associated molecules consisting of ABCF1, CORO1C, DPP3, PREB, UBE3A, and PTDSS1 in a lung tumor or breast tumor sample obtained from a subject.
Measurement of expression by quantitative molecular techniques
Expression of ABCF1, CORO1C, DPP3, PREB, UBE3A, and PTDSS1 is measured by real-time quantitative polymerase chain reaction or microarray analysis.
Detection including housekeeping genes
The method can further include detecting expression of one to ten housekeeping genes to serve as controls.
Detection of 6 to 17 cancer survival factor-associated molecules including the six core genes
Detecting expression of a group of 6 to 17 cancer survival factor-associated molecules selected from a specified list, where this group includes the six genes ABCF1, CORO1C, DPP3, PREB, UBE3A, and PTDSS1, in a lung or breast tumor sample from a subject.
Comparison to a non-tumor control
The method further comprises comparing expression levels of the cancer survival factor-associated molecules in the tumor sample to a non-tumor control sample to assess differential expression indicative of prognosis or diagnosis.
The claims cover methods of detecting specific cancer survival factor-associated molecules in lung or breast tumor samples, focusing on a defined 6-gene signature or a larger set including these genes, using quantitative molecular techniques, optionally with housekeeping gene controls, and comparing expression to controls for cancer diagnosis or prognosis.
Stated Advantages
The gene expression signatures are highly predictive of survival outcomes and applicable to multiple tumor types.
The six-gene signature enables a rapid and inexpensive hospital-based assay compared to currently available expensive assays.
The signatures reliably predict survival including metastasis-free survival, helping select patients for suitable treatment consistent with the disease progression.
Documented Applications
Determining the prognosis of subjects with tumors such as breast tumors or lung tumors, including predicting survival outcomes and distinguishing benign from malignant tumors.
Treating cancer patients by administering agents that alter expression or activity of one or more cancer survival factor-associated genes.
Using arrays with probes or antibodies specific for cancer survival factor-associated genes or proteins for diagnostics or prognostics.
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