Biomarkers for Bladder Cancer

• US 20080026410A1
• Filed: 07/20/2005
• Published: 01/31/2008
• Est. Priority Date: 12/02/2004
• Status: Abandoned Application

• Current Assignee: Eastern Virginia Medical School
• Original Assignee: Eastern Virginia Medical School
• Inventors: Vlahou, Antonia
• Application Number:
  US11/632,423
• Publication Number:
  US 20080026410A1
• Time in Patent Office: Days
• US Class Current: 435/7.23
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 48/005 characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/52 Cytokines; Lymphokines; Interferons
• CPC Class Codes: C07K 14/54 Interleukins [IL]
• CPC Class Codes: C07K 16/244 Interleukins [IL]
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/10343 viral genome or elements thereof as genetic vector
• CPC Class Codes: G01N 33/5011 for testing antineoplastic activity

Abstract

The present invention provides protein-based biomarkers and biomarker combinations that are useful in qualifying bladder cancer status in a patient. In particular, the biomarkers of this invention are useful to classify a subject sample as bladder cancer or non-bladder cancer. The biomarkers can be detected by SELDI mass spectrometry.

Claims

1. A method for qualifying bladder cancer status in a subject comprising:

a) measuring at least one biomarker in a biological sample from the subject, wherein the at least one biomarker is selected from the group consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, and Marker 12; and

b) correlating the measurement with bladder cancer status.

2. The method of claim 1, comprising measuring a plurality of said biomarkers.

3. The method of claim 2, wherein the plurality comprises at least 3 biomarkers.

4. The method of claim 2, wherein the plurality comprises at least 4 biomarkers.

5. The method of claim 1, further comprising measuring Marker 13.

6. The method of claim 1, further comprising measuring Marker 14.

7. The method of claim 1, further comprising measuring Marker 15.

8. The method of claim 1, further comprising measuring Marker 16.

9. The method of claim 1, further comprising measuring Marker 17.

10. The method of claim 1, further comprising measuring Marker 18.

12. The method of any of claims 1 or 11, wherein the at least one biomarker is measured by capturing the biomarker on an adsorbent surface of a SELDI probe and detecting the captured biomarkers by laser desorption-ionization mass spectrometry.

13. The method of any of claims 1 or 11, wherein the at least one biomarker is measured by immunoassay.

14. The method of any of claims 1 or 11, wherein the sample is urine.

15. The method of any of claims 1 or 11, wherein the sample is serum.

16. The method of any of claims 1 or 11, wherein the correlating is performed by a software classification algorithm.

17. The method of any of claims 1 or 11, wherein bladder cancer status is selected from bladder cancer and non-bladder cancer.

18. The method of any of claims 1 or 11, further comprising (c) managing subject treatment based on the status.

19. The method of claim 12, wherein the adsorbent is a cation exchange adsorbent.

20. The method of claim 12, wherein the adsorbent is a biospecific adsorbent.

21. The method of claim 18, further comprising (d) measuring the at least one biomarker after subject management.

11. A method for qualifying bladder cancer status in a subject comprising:

a) measuring a plurality of biomarkers in a biological sample from the subject, wherein at least one biomarker is selected from the group consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, and Marker 12 and at least one biomarker is selected from the group consisting of Marker 13, Marker 14, Marker 15, Marker 16, Marker 17, and Marker 18; and

b) correlating the measurement with bladder cancer status.

22. A method comprising measuring at least one biomarker in a sample from a subject, wherein the at least one biomarker is selected from the group consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, and Marker 12.

23. The method of claim 22, comprising measuring a plurality of said biomarkers.

24. The method of claim 23, wherein the plurality comprises at least 3 biomarkers.

25. The method of claim 23, wherein the plurality comprises at least 4 biomarkers.

26. The method of claim 22, further comprising measuring Marker 13.

27. The method of claim 22, further comprising measuring Marker 14.

28. The method of claim 22, further comprising measuring Marker 15.

29. The method of claim 22, further comprising measuring Marker 16.

30. The method of claim 22, further comprising measuring Marker 17.

31. The method of claim 22, further comprising measuring Marker 18.

33. The method of any of claims 22 or 32, wherein the biomarker is measured by capturing the biomarker on an adsorbent surface of a SELDI probe and detecting the captured biomarkers by laser desorption-ionization mass spectrometry.

34. The method of any of claims 22 or 32, wherein the sample is urine.

35. The method of any of claims 22 or 32, wherein the sample is serum.

36. The method of claim 33, wherein the adsorbent is a cation exchange adsorbent.

37. The method of claim 33, wherein the adsorbent is a biospecific adsorbent.

32. A method comprising measuring a plurality of biomarkers in a sample from a subject, wherein at least one biomarker is selected from the group consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, and Marker 12 and at least one biomarker is selected from the group consisting of Marker 13, Marker 14, Marker 15, Marker 16, Marker 17, and Marker 18.

38. A kit comprising:

a) a solid support comprising at least one capture reagent attached thereto, wherein the capture reagent binds at least one biomarker selected from the group consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, and Marker 12; and

b) instructions for using the solid support to detect the at least one biomarker.

39. The kit of claim 38, comprising instructions for using the solid support to detect a plurality of said biomarkers.

40. The kit of claim 39, wherein the plurality comprises at least 3 biomarkers.

41. The kit of claim 39, wherein the plurality comprises at least 4 biomarkers.

42. The kit of claim 38, further comprising instructions for using the solid support to Marker 13.

43. The kit of claim 38, further comprising instructions for using the solid support to detect Marker 14.

44. The kit of claim 38, further comprising instructions for using the solid support to detect Marker 15.

45. The kit of claim 38, further comprising instructions for using the solid support to detect Marker 16.

46. The kit of claim 38, further comprising instructions for using the solid support to detect Marker 17.

47. The kit of claim 38, further comprising instructions for using the solid support to detect Marker 18.

49. The kit of any of claims 38 or 48, wherein the solid support comprising a capture reagent is a SELDI probe.

50. The kit of any of claims 38 or 48, additionally comprising (c) an anion exchange chromatography adsorbent.

51. The kit of claim 49, wherein the capture reagent is a cation exchange adsorbent.

48. A kit comprising:

a) a solid support comprising at least one capture reagent attached thereto, wherein the capture reagent binds a plurality of biomarkers, wherein at least one biomarker is selected from the group consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, and Marker 12 and at least one biomarker is selected from the group consisting of Marker 13, Marker 14, Marker 15, Marker 16, Marker 17, and Marker 18; and

b) instructions for using the solid support to detect the plurality of biomarkers.

52. A kit comprising:

a) a solid support comprising at least one capture reagent attached thereto, wherein the capture reagents bind at least one biomarker selected from the group consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, and Marker 12; and

b) a container containing at least one of the biomarkers.

53. The kit of claim 52, wherein the container comprises a plurality of said biomarkers.

54. The kit of claim 53, wherein the plurality comprises at least 3 biomarkers.

55. The kit of claim 53, wherein the plurality comprises at least 4 biomarkers.

56. The kit of claim 52, further comprising instructions for using the solid support to detect Marker 13.

57. The kit of claim 52, further comprising instructions for using the solid support to detect Marker 14.

58. The kit of claim 52, further comprising instructions for using the solid support to detect Marker 15.

59. The kit of claim 52, further comprising instructions for using the solid support to detect Marker 16.

60. The kit of claim 52, further comprising instructions for using the solid support to detect Marker 17.

61. The kit of claim 52, further comprising instructions for using the solid support to detect Marker 18.

63. The kit of any of claims 52 or 62, wherein the solid support comprising a capture reagent is a SELDI probe.

64. The kit of any of claims 52 or 62, additionally comprising (c) an anion exchange chromatography adsorbent.

65. The kit of claim 63, wherein the capture reagent is a cation exchange adsorbent.

62. A kit comprising:

a) a solid support comprising at least one capture reagent attached thereto, wherein the capture reagents bind a plurality of biomarkers, wherein at least one biomarker is selected from the group consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, and Marker 12 and at least one biomarker is selected from the group consisting of Marker 13, Marker 14, Marker 15, Marker 16, Marker 17, and Marker 18; and

b) a container containing at least one of the biomarkers.

66. A software product comprising:

a) code that accesses data attributed to a sample, the data comprising measurement of at least one biomarker in the sample, the biomarker selected from the group consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, and Marker 12; and

b) code that executes a classification algorithm that classifies the bladder cancer status of the sample as a function of the measurement.

67. The software product of claim 66, wherein the classification algorithm classifies the bladder cancer status of the sample as a function of the measurement of a plurality of said biomarkers.

68. The software product of claim 67, wherein the plurality comprises at least 3 biomarkers.

69. The software product of claim 67, wherein the plurality comprises at least 4 biomarkers.

70. The software product of claim 66, wherein the classification algorithm classifies the bladder cancer status of the sample further as a function of the measurement of Marker 13.

71. The software product of claim 66, wherein the classification algorithm classifies the bladder cancer status of the sample further as a function of the measurement of Marker 14.

72. The software product of claim 66, wherein the classification algorithm classifies the bladder cancer status of the sample further as a function of the measurement of Marker 15.

73. The software product of claim 66, wherein the classification algorithm classifies the bladder cancer status of the sample further as a function of the measurement of Marker 16.

74. The software product of claim 66, wherein the classification algorithm classifies the bladder cancer status of the sample further as a function of the measurement of Marker 17.

75. The software product of claim 66, wherein the classification algorithm classifies the bladder cancer status of the sample further as a function of the measurement of Marker 18.

76. A software product comprising:

a) code that accesses data attributed to a sample, the data comprising measurement of a plurality of biomarkers in the sample, and wherein at least one biomarker is selected from the group consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, and Marker 12 and at least one biomarker is selected from the group consisting of Marker 13, Marker 14, Marker 15, Marker 16, Marker 17, and Marker 18; and

b) code that executes a classification algorithm that classifies the bladder cancer status of the sample as a function of the measurement.

77. A purified biomolecule selected from the group of biomarkers consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, and Marker 12.

78. A method comprising detecting a biomarker selected from the group consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, and Marker 12 by mass spectrometry or immunoassay.

79. A method comprising detecting a plurality of biomarkers by mass spectrometry or immunoassay, wherein at least one biomarker is selected from the group consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, and Marker 12 and at least one biomarker is selected from the group consisting of Marker 13, Marker 14, Marker 15, Marker 16, Marker 17, and Marker 18.

80. A method comprising communicating to a subject a diagnosis relating to bladder cancer status determined from the correlation of biomarkers in a sample from the subject, wherein at least one biomarker is selected from the group consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, and Marker 12.

82. The method of any of claims 80 or 81, wherein the diagnosis is communicated to the subject via a computer-generated medium.

81. A method comprising communicating to a subject a diagnosis relating to bladder cancer status determined from the correlation of a plurality of biomarkers in a sample from the subject, wherein at least one biomarker is selected from the group consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, and Marker 12 and at least one biomarker is selected from the group consisting of Marker 13, Marker 14, Marker 15, Marker 16, Marker 17, and Marker 18.

83. A method for identifying a compound that interacts with any of the biomarkers selected from the group consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, and Marker 12, wherein said method comprises:

a) contacting the biomarker with a test compound; and

b) determining whether the test compound interacts with the biomarker.

84. A method for modulating the concentration of a biomarker selected from the group consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, Marker 12, Marker 13, Marker 14, Marker 15, Marker 16, Marker 17, and Marker 18 in a cell, wherein said method comprises:

a) contacting said cell with a protease inhibitor, wherein said protease inhibitor prevents cleavage of said biomarker.

85. A method of treating a condition in a subject, wherein said method comprises administering to a subject a therapeutically effective amount of a compound which modulates the expression or activity of a protease which cleaves a biomarker selected from the group consisting of Marker 1, Marker 2, Marker 3, Marker 4, Marker 5, Marker 6, Marker 7, Marker 8, Marker 9, Marker 10, Marker 11, Marker 12, Marker 13, Marker 14, Marker 15, Marker 16, Marker 17, and Marker 18.

86. The method of claim 85, wherein said condition is bladder cancer.