Prostate cancer diagnosis and outcome prediction by expression analysis
AssigneeWhitehead Institute for Biomedical Research
InventorsTodd R. Golub, Phillip G. Febbo, Kenneth N. Ross, William R. Sellers
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Abstract
Methods identifying prostate cancer, methods for prognosing and diagnosing prostate cancer, methods for identifying a compound that modulates prostate cancer development, methods for determining the efficacy of a prostate cancer therapy, and oligonucleotide microarrays containing probes for genes involved in prostate cancer development are described.
Claims17
A method of identifying prostate cancer comprising the steps of:
- a) obtaining a sample derived from prostate tissue;
- and
- b) determining a gene expression profile from a gene expression product of at least one prostate cancer identification informative gene having increased expression in prostate cancer relative to a control,
- wherein increased expression of said gene expression product in said sample is indicative of prostate cancer.
A method of identifying prostate cancer comprising the steps of:
- a) obtaining a sample derived from prostate tissue;
- and
- b) determining a gene expression profile from a gene expression product of at least one prostate cancer identification informative gene having decreased expression in prostate cancer relative to a control,
- wherein decreased expression of said gene expression product in said sample is indicative of prostate cancer.
A method of identifying a compound for use in modulating prostate cancer development, said method comprising the steps of:
- a) providing a cell or cell lysate sample;
- b) contacting the cell or cell lysate sample with a candidate compound;
- and
- c) detecting an increase in expression of at least one informative gene having decreased expression in prostate cancer,
- wherein a candidate compound that increases the expression of said informative gene is a compound for use in modulating prostate cancer development.
A method of identifying a compound for use in modulating prostate cancer development, said method comprising the steps of:
- a) providing a cell or cell lysate sample;
- b) contacting the cell or cell lysate sample with a candidate compound;
- and
- c) detecting a decrease in expression of at least one informative gene having increased expression in prostate cancer,
- wherein a candidate compound that decreases the expression of said informative gene is a compound for use in modulating prostate cancer development.
A method of predicting the likelihood of prostate cancer development in a subject, comprising the steps of:
- a) obtaining a sample derived from prostate tissue of a subject;
- b) determining a gene expression profile from a gene expression product of at least one informative gene having increased expression in prostate cancer relative to a control;
- wherein increased expression of said gene in said sample indicates an increased likelihood of prostate cancer development in the subject.
A method of predicting the likelihood of prostate cancer development in a subject, comprising the steps of:
- a) obtaining a sample derived from prostate tissue of a subject;
- b) determining a gene expression profile from a gene expression product of at least one informative gene having decreased expression in prostate cancer relative to a control;
- wherein decreased expression of said gene in said sample indicates an increased likelihood of prostate cancer development in said subject.
A method of diagnosing prostate cancer in a subject, comprising the steps of:
- a) obtaining a sample derived from prostate tissue of a subject;
- b) determining a gene expression profile from a gene expression product of at least one informative gene having increased expression in prostate cancer relative to a control,
- wherein increased expression of said gene in said sample indicates the presence of prostate cancer in said subject.
A method of diagnosing prostate cancer in a subject, comprising the steps of:
- a) obtaining a sample derived from prostate tissue of a subject;
- b) determining a gene expression profile from a gene expression product of at least one informative gene having decreased expression in prostate cancer relative to a control,
- wherein decreased expression of said gene in said sample indicates the presence of prostate cancer in said subject.
A method of classifying a prostate tumor sample according to predicted treatment outcome comprising the steps of:
- a) isolating a gene expression product from at least one informative gene from a cell in a sample;
- and
- b) determining a gene expression profile of at least one informative gene, said informative gene selected from the group consisting of genes having decreased expression in prostate cancer relative to a control and genes having increased expression in prostate cancer relative to a control,
- wherein the gene expression profile is correlated with a treatment outcome, thereby classifying the sample with respect to treatment outcome.
A method of assessing efficacy of treatment of prostate cancer in a subject having prostate cancer comprising the steps of:
- a) obtaining a sample derived from an organ or tissue of a subject;
- b) determining a gene expression profile from a gene expression product of at least one informative gene having increased expression in prostate cancer relative to a control, and
- c) repeating steps a) and b) at one or more time points during treatment,
- wherein decreased expression of said gene in said sample over time indicates an effective treatment.
A method of assessing efficacy of treatment of prostate cancer in a subject having prostate cancer comprising the steps of:
- a) obtaining a sample derived from an organ or tissue of a subject;
- b) determining a gene expression profile from a gene expression product of at least one informative gene having increased expression in prostate cancer relative to a control, and
- c) repeating steps a) and b) at one or more time points during treatment,
- wherein a lack of decreased expression of said gene in said sample over time indicates a less effective treatment.
A method of assessing efficacy of treatment of prostate cancer in a subject having prostate cancer comprising the steps of:
- a) obtaining a sample derived from an organ or tissue of a subject;
- b) determining a gene expression profile from a gene expression product of at least one informative gene having decreased expression in prostate cancer relative to a control, and
- c) repeating steps a) and b) at one or more time points during treatment,
- wherein increased expression of said gene in said sample over time indicates an effective treatment.
A method of assessing efficacy of treatment of prostate cancer in a subject having prostate cancer comprising the steps of:
- a) obtaining a sample derived from an organ or tissue of a subject;
- b) determining a gene expression profile from a gene expression product of at least one informative gene having decreased expression in prostate cancer relative to a control, and
- c) repeating steps a) and b) at one or more time points during treatment,
- wherein alack of increased expression of said gene in said sample over time indicates a less effective treatment.
An oligonucleotide microarray having immobilized thereon a plurality of oligonucleotide probes specific for one or more informative genes selected from the group consisting of the genes in FIGS. 2A-N, FIGS. 3A-3C2, FIGS. 9A-9D, FIGS. 9E-9L, FIG. 10A, FIG. 10B, FIGS. 14A-14B, FIGS. 14C-14E, Platelet Derived Growth Factor Receptor, Beta Chromogranin A, HOXC6, Inositol Triphosphate Receptor Type 3, and Beta Galactoside Sialotransferase.
A method of identifying a compound that decreases expression of an informative gene having increased expression in prostate cancer, said method comprising the steps of:
- a) providing a nucleic acid molecule comprising a promoter region of the informative gene, or part of said promoter region, operably linked to a reporter gene;
- b) contacting the nucleic acid molecule with a candidate compound;
- and
- c) assessing the level of the reporter gene,
- wherein a candidate compound that decreases expression of the reporter gene relative to a control is a compound that decreases expression of the informative gene having increased expression in prostate cancer.
A method of identifying a compound that increases expression of an informative gene having decreased expression in prostate cancer, said method comprising the steps of:
- a) providing a nucleic acid molecule comprising a promoter region of the informative gene, or part of said promoter region, operably linked to a reporter gene;
- b) contacting the nucleic acid molecule with a candidate compound;
- and
- c) assessing the level of the reporter gene,
- wherein a candidate compound that increases expression of the reporter gene relative to a control is a compound that increases expression of the informative gene having decreased expression in prostate cancer.
A method of identifying a polypeptide that interacts with an informative gene expression product having modulated expression in prostate cancer in a yeast two-hybrid system, said method comprising the steps of:
- a) providing a first nucleic acid vector comprising a nucleic acid molecule encoding a DNA binding domain and a polypeptide encoded by the informative gene that is increased or decreased in prostate cancer;
- b) providing a second nucleic acid vector comprising a nucleic acid encoding a transcription activation domain and a nucleic acid encoding a test polypeptide;
- c) contacting the first nucleic acid vector with the second nucleic acid vector in a yeast two-hybrid system;
- and
- d) assessing transcriptional activation in the yeast two-hybrid system,
- wherein an increase in transcriptional activation relative to a control indicates that the test polypeptide is a polypeptide that interacts with the informative gene expression product having modulated expression in prostate cancer.
Dependencies are inferred from the claim text.