GENE SIGNATURES FOR CANCER DIAGNOSIS AND PROGNOSIS
Biomarkers and methods using the biomarkers for molecular detection and classification of disease and, particularly, molecular markers for cancer diagnosis and prognosis and methods of use thereof are provided.
1 . A method of determining gene expression in a tumor sample, comprising:
obtaining a patient sample;
determining the expression levels of a panel of genes in said tumor sample including at least 4 cell-cycle progression genes; and
providing a test value by (1) weighting the determined expression of each of a plurality of test genes selected from said panel of genes with a predefined coefficient, and (2) combining the weighted expression to provide said test value, wherein at least 75%, at least 85% or at least 95% of said plurality of test genes are cell-cycle progression genes.
2 . The method of claim 1 , wherein said sample is a tumor sample from a patient identified as having prostate cancer, lung cancer, bladder cancer or brain cancer.
3 . The method of claim 1 , wherein at least 90% of said plurality of test genes are cell-cycle progression genes.
4 . The method of claim 1 , wherein said determining step comprises:
measuring the amount of mRNA in said tumor sample transcribed from each of between 6 and 200 cell-cycle progression genes; and
measuring the amount of mRNA of one or more housekeeping genes in said tumor sample.
5 . The method of claim 1 , wherein the expression of at least 8 cell-cycle progression genes are determined and weighted.
6 . A method of diagnosing cancer in a patient comprising:
determining in a sample the expression of a panel of genes including at least 4 cell-cycle progression genes;
providing a test value by (1) weighting the determined expression of each of a plurality of test genes selected from said panel of genes with a predefined coefficient, and (2) combining the weighted expression to provide said test value, wherein at least 75%, at least 85% or at least 95% of said plurality of test genes are cell-cycle progression genes, wherein an increased level of expression of said plurality of test genes indicates said patient has cancer.
7 . A method of prognosing prostate cancer, lung cancer, bladder cancer or brain cancer, comprising:
determining in a tumor sample from a patient diagnosed of prostate cancer, lung cancer, bladder cancer or brain cancer, the expression of a panel of genes in said tumor sample including at least 4 cell-cycle progression genes;
providing a test value by (1) weighting the determined expression of each of a plurality of test genes selected from said panel of genes with a predefined coefficient, and (2) combining the weighted expression to provide said test value, wherein at least 75%, at least 85% or at least 95% of said plurality of test genes are cell-cycle progression genes, wherein an increased level of expression of said plurality of test genes indicates a poor prognosis.
8 . The method of claim 6 , further comprising comparing said test value to a reference value, and correlating to the patient having cancer if said test value is greater than said reference value.
9 . The method of claim 7 , further comprising comparing said test value to a reference value, and correlating to an increased likelihood of poor prognosis if said test value is greater than said reference value.
10 . The method of claim 6 , wherein the expression levels of from 6 to about 200 cell-cycle progression genes are measured.
11 . The method of claim 6 , wherein said determining step comprises:
measuring the amount of mRNA of from 6 to about 200 cell-cycle progression genes in said tumor sample; and
measuring the amount of mRNA of one or more housekeeping genes in said tumor sample.
12 - 35 . (canceled)
36 . The method of claim 1 , wherein said cell-cycle progression genes are weighted to contribute at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or 100% of the total weight given to all of said plurality of test genes.
37 - 39 . (canceled)