Claims
- 1. A method for diagnosing the presence of cancer cells or non-cancer cells in a tissue sample, comprising
providing a set of two or more genes, wherein the set comprises at least one upregulated gene that is expressed in greater amounts in the cancer cells than in corresponding non-cancer cells and at least one downregulated gene that is expressed in lesser amounts in cancer cells than in corresponding non-cancer cells, determining the expression levels of the set of two or more genes, calculating at least one ratio of the expression level of the at least one upregulated gene to the expression level of the at least one downregulated gene, wherein the at least one ratio is indicative of the presence of cancer cells or non-cancer cells in the tissue sample.
- 2. The method of claim 1, wherein there is at least a 2-fold difference in mean expression levels between the at least one upregulated gene and the at least one downregulated gene.
- 3. The method of claim 1, wherein two or more expression ratios are calculated.
- 4. The method of claim 3, further comprising combining the two or more expression ratios.
- 5. The method of claim 4, wherein the step of combining the two or more expression ratios comprises calculating the geometric mean of the two or more expression ratios.
- 6. The method of claim 1, wherein the ratio is calculated by division of the expression level of one upregulated gene by the expression level of one downregulated gene.
- 7. The method of claim 1, wherein the ratio is calculated by division of the expression levels of two or more upregulated genes by the expression level of one downregulated gene.
- 8. The method of claim 1, wherein the ratio is calculated by division of the expression level of one upregulated gene by the expression levels of two or more downregulated genes.
- 9. The method of claim 1, wherein the ratio is calculated by division of the expression levels of two or more upregulated genes by the expression levels of two or more downregulated genes.
- 10. The method of claim 1, further comprising transforming the expression level data for the upregulated and/or downregulated genes prior to calculating the ratio.
- 11. The method of claim 1, wherein the expression levels are determined by a method selected from the group consisting of nucleic acid hybridization and nucleic acid amplification.
- 12. The method of claim 11, wherein the nucleic acid hybridization is performed using a solid-phase nucleic acid molecule array.
- 13. The method of claim 11, wherein the nucleic acid amplification method is real-time PCR.
- 14. The method of claim 1, wherein the expression levels are determined by an immunological method.
- 15. The method of claim 14, wherein the immunological method is performed using a solid-phase antibody array.
- 16. The method of claim 14, wherein the immunological method is an ELISA or ELISPOT assay.
- 17. The method of claim 1, wherein the cancer is selected from the group consisting of malignant pleural mesothelioma, lung adenocarcinoma, squamous carcinoma, medulloblastoma, prostate cancer, breast cancer, diffuse large B-cell lymphoma, follicular lymphoma and ovarian cancer.
- 18. The method of claim 1, wherein the at least one ratio is indicative of the presence of cancer cells in the tissue sample.
- 19. The method of claim 1, wherein the at least one ratio is indicative of the presence of non-cancer cells in the tissue sample.
- 20. A method for determining prognosis or outcome of a cancer patient, comprising
providing a set of two or more genes, wherein the set comprises at least one upregulated gene that is expressed in greater amounts in a tumor sample from a cancer patient having a good prognosis or outcome than in a tumor sample from a cancer patient having a poor prognosis or outcome and at least one downregulated gene that is expressed in lesser amounts in the tumor sample from the cancer patient having a good prognosis or outcome than in the tumor sample from the cancer patient having a poor prognosis or outcome, determining the expression levels of the set of two or more genes, calculating at least one ratio of the expression level of the at least one upregulated gene to the expression level of the at least one downregulated gene, wherein the at least one ratio is indicative of the prognosis or outcome of the cancer patient.
- 21. The method of claim 20, wherein there is at least a 2-fold difference in mean expression levels between the at least one upregulated gene and the at least one downregulated gene.
- 22. The method of claim 20, wherein two or more expression ratios are calculated.
- 23. The method of claim 22, further comprising combining the two or more expression ratios.
- 24. The method of claim 23, wherein the step of combining the two or more expression ratios comprises calculating the geometric mean of the two or more expression ratios.
- 25. The method of claim 20, wherein the ratio is calculated by division of the expression level of one upregulated gene by the expression level of one downregulated gene.
- 26. The method of claim 20, wherein the ratio is calculated by division of the expression levels of two or more upregulated genes by the expression level of one downregulated gene.
- 27. The method of claim 20, wherein the ratio is calculated by division of the expression level of one upregulated gene by the expression levels of two or more downregulated genes.
- 28. The method of claim 20, wherein the ratio is calculated by division of the expression levels of two or more upregulated genes by the expression levels of two or more downregulated genes.
- 29. The method of claim 20, further comprising transforming the expression level data for the upregulated and/or downregulated genes prior to calculating the ratio.
- 30. The method of claim 20, wherein the expression levels are determined by a method selected from the group consisting of nucleic acid hybridization and nucleic acid amplification.
- 31. The method of claim 30, wherein the nucleic acid hybridization is performed using a solid-phase nucleic acid molecule array.
- 32. The method of claim 30, wherein the nucleic acid amplification method is real-time PCR.
- 33. The method of claim 20, wherein the expression levels are determined by an immunological method.
- 34. The method of claim 33, wherein the immunological method is performed using a solid-phase antibody array.
- 35. The method of claim 33, wherein the immunological method is an ELISA or ELISPOT assay.
- 36. The method of claim 20, wherein the cancer is selected from the group consisting of malignant pleural mesothelioma, lung adenocarcinoma, squamous carcinoma, medulloblastoma, prostate cancer, breast cancer, diffuse large B-cell lymphoma, follicular lymphoma and ovarian cancer.
- 37. A kit for cancer diagnosis comprising,
a set of one or more ratios applicable to the analysis of gene expression data, wherein the ratio is calculated from the expression levels of at least one upregulated gene that is expressed in greater amounts in the cancer cells than in corresponding non-cancer cells and at least one downregulated gene that is expressed in lesser amounts in cancer cells than in corresponding non-cancer cells.
- 38. The kit of claim 37, further comprising instructions for the use of the one or more ratios in the diagnosis of the presence of cancer cells or non-cancer cells in a biological sample.
- 39. A cancer diagnostic system comprising
a measurement device that measures gene expression level data of a set of two or more genes, wherein the set comprises at least one upregulated gene that is expressed in greater amounts in the cancer cells than in corresponding non-cancer cells and at least one downregulated gene that is expressed in lesser amounts in cancer cells than in corresponding non-cancer cells, a data transformation device that acquires the gene expression data from the measurement device and performs data transformation to calculate a ratio of the gene expression levels of the upregulated and downregulated genes.
- 40. The cancer diagnostic system of claim 39, wherein data transformation device selects gene expression data of a selected set of genes from the measurement device for calculating the ratio of the selected set of genes, wherein the ratio calculated from the gene expression data of the selected set of genes is diagnostic for a selected cancer.
- 41. The cancer diagnostic system of claim 39, further comprising a user interface output device to output the ratio to a user.
- 42. The cancer diagnostic system of claim 41, further comprising a database of ratios of gene expression that are diagnostic for cancers, and a comparison device that compares the ratio calculated from the measured gene expression to the diagnostic ratios stored in the database and outputs the comparison to the user interface output device.
- 43. The cancer diagnostic system of claim 41, further comprising a database of treatment information for specific cancers, wherein the comparison device identifies treatment information in the database for the specific cancer for which the diagnostic ratio matches the, calculated ratio, and wherein the comparison outputs the treatment information to the user interface output device.
- 44. A method for diagnosing malignant pleural mesothelioma in a subject suspected of having malignant pleural mesothelioma comprising:
obtaining from the subject a tissue sample suspected of being cancerous, determining the expression of a set of nucleic acid molecules or expression products thereof in the tissue sample, wherein the set of nucleic acid molecules comprises at least two nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77.
- 45. The method of claim 44, wherein the set of nucleic acid molecules comprises at least 3 nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77.
- 46. The method of claim 44, wherein the set includes at least 4 nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77.
- 47. The method of claim 44, wherein the set includes at least 5 nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77.
- 48. The method of claim 44, wherein the set includes at least 10 nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77.
- 49. The method of claim 44, wherein the set includes at least 12 nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77.
- 50. The method of claim 44, wherein the set includes at least 15 nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77.
- 51. The method of claim 44, wherein the set includes at least 20 nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77.
- 52. The method of claim 44, wherein the set includes at least 25 nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77.
- 53. The method of claim 44, further comprising:
determining the expression of the set of nucleic acid molecules or expression products thereof in a non-cancerous tissue sample, and comparing the expression of the set of nucleic acid molecules or expression products thereof in the tissue sample suspected of being cancerous and the non-cancerous tissue sample.
- 54. The method of claim 44, further comprising calculating a ratio of the expression of at least two genes among the set of nucleic acid molecules.
- 55. A method for selecting a course of treatment of a subject having or suspected of having malignant pleural mesothelioma, comprising:
obtaining from the subject a tissue sample suspected of being cancerous, determining the expression of a set of nucleic acid markers or expression products thereof which are differentially expressed in malignant pleural mesothelioma tumor tissue samples, and selecting a course of treatment appropriate to the malignant pleural mesothelioma of the subject.
- 56. The method of claim 55, further comprising calculating a ratio of the expression of at least two genes among the set of nucleic acid markers or expression products thereof.
- 57. The method of claim 55, further comprising:
determining the expression of the set of nucleic acid molecules or expression products thereof in a non-cancerous tissue sample.
- 58. The method of claim 55, wherein the expression of a set of nucleic acid markers is determined by a method selected from the group consisting of nucleic acid hybridization and nucleic acid amplification.
- 59. The method of claim 58, wherein the nucleic acid hybridization is performed using a solid-phase nucleic acid molecule array.
- 60. The method of claim 58, wherein the nucleic acid amplification method is real-time PCR.
- 61. A method for evaluating treatment of malignant pleural mesothelioma, comprising:
obtaining a first determination of the expression of a set of nucleic acid molecules, or expression products thereof, which are differentially expressed in a malignant pleural mesothelioma tumor tissue sample from a subject undergoing treatment for cancer, obtaining a second determination of the expression of the set of nucleic acid molecules, or expression products thereof, in a second malignant pleural mesothelioma tumor tissue sample from the subject after obtaining the first determination, comparing the first determination of expression to the second determination of expression as an indication of evaluation of the treatment.
- 62. The method of claim 61, wherein the determinations of expressions are used to calculate at least one ratio of gene expression.
- 63. The method of claim 61, further comprising:
determining the expression of a set of nucleic acid markers which are differentially expressed in non-cancerous tissue samples.
- 64. The method of claim 61, wherein the expression of a set of nucleic acid markers is determined by a method selected from the group consisting of nucleic acid hybridization and nucleic acid amplification.
- 65. The method of claim 64, wherein the nucleic acid hybridization is performed using a solid-phase nucleic acid molecule array.
- 66. The method of claim 64, wherein the nucleic acid amplification method is real-time PCR.
- 67. A solid-phase nucleic acid molecule array consisting essentially of at least two nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77 fixed to a solid substrate.
- 68. The solid-phase nucleic acid molecule array of claim 67, further comprising at least one control nucleic acid molecule.
- 69. The solid-phase nucleic acid molecule array of claim 67, wherein the set of nucleic acid molecules comprises at least 3 nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77.
- 70. The solid-phase nucleic acid molecule array of claim 67, wherein the set includes at least 4 nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77.
- 71. The solid-phase nucleic acid molecule array of claim 67, wherein the set includes at least 5 nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77.
- 72. The solid-phase nucleic acid molecule array of claim 67, wherein the set includes at least 10 nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77.
- 73. The solid-phase nucleic acid molecule array of claim 67, wherein the set includes at least 12 nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77.
- 74. The solid-phase nucleic acid molecule array of claim 67, wherein the set includes at least 15 nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77.
- 75. The solid-phase nucleic acid molecule array of claim 67, wherein the set includes at least 20 nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77.
- 76. The solid-phase nucleic acid molecule array of claim 67, wherein the set includes at least 25 nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77.
- 77. A solid-phase protein microarray comprising at least two antibodies or antigen-binding fragments thereof, that specifically bind at least two different polypeptides selected from the group consisting of SEQ ID NOs:10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, fixed to a solid substrate.
- 78. The protein microarray of claim 77, further comprising at least one control polypeptide molecule.
- 79. The protein microarray of claim 77, wherein the antibodies are monoclonal antibodies.
- 80. The protein microarray of claim 77, wherein the antibodies are polyclonal antibodies.
- 81. A method for identifying lead compounds for a pharmacological agent useful in the treatment of malignant pleural mesothelioma, comprising:
contacting a malignant pleural mesothelioma cell or tissue with a candidate pharmacological agent, determining the expression of a set of nucleic acid molecules in the malignant pleural mesothelioma cell or tissue sample under conditions which, in the absence of the candidate pharmacological agent, permit a first amount of expression of the set of nucleic acid molecules wherein the set of nucleic acid molecules comprises at least two nucleic acid molecules selected from the group consisting of SEQ ID NOs:9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, and detecting a test amount of the expression of the set of nucleic acid molecules, wherein a decrease in the test amount of expression in the presence of the candidate pharmacological agent relative to the first amount of expression indicates that the candidate pharmacological agent is a lead compound for a pharmacological agent which is useful in the treatment of malignant pleural mesothelioma.
- 82. The method of claim 81, further comprising calculating a ratio of gene expression.
RELATED APPLICATIONS
[0001] This application claims the benefit under 35 U.S.C. §119(e) of U.S. provisional application No. 60/317,389, filed Sep. 5, 2001, and U.S. provisional application 60/______, filed Aug. 30, 2002, the entire disclosures of which are incorporated herein by reference.
GOVERNMENT SUPPORT
[0002] This invention was made in part with government support under grant number DK58849 from the National Institutes of Health. The United States government may have certain rights in this invention.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60317389 |
Sep 2001 |
US |
|
60407431 |
Aug 2002 |
US |