METHODS FOR DIAGNOSIS AND PROGNOSIS OF EPITHELIAL CANCERS

• US 20080064047A1
• Filed: 07/27/2007
• Published: 03/13/2008
• Est. Priority Date: 01/28/2005
• Status: Abandoned Application

• Current Assignee: Children's Medical Center Corporation, The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Feldman, Adam, Zetter, Bruce, McDougal, W.
• Application Number:
  US11/829,323
• Publication Number:
  US 20080064047A1
• Time in Patent Office: Days
• US Class Current: 435/7.9
• CPC Class Codes: G01N 2333/8139 Cysteine protease (E.C. 3.4.22) inhibitors, e.g. cystatin
• CPC Class Codes: G01N 33/57407 Specifically defined cancers
• CPC Class Codes: G01N 33/57488 involving compounds identifable in body fluids
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

The present invention is based on the discovery that three proteins, Cystatin B, Chaperonin 10, and Profilin are present in the urine of patients with bladder cancer, a cancer of epithelial origin. Accordingly, the present invention is directed to methods for prognostic evaluation of cancers of epithelial origin and to methods for facilitating diagnosis of cancers of epithelial origin by monitoring the presence of these markers in biological samples. The invention is also directed to markers for therapeutic efficacy.

Claims

1. A method for facilitating the diagnosis of a patient for a cancer of epithelial origin comprising:

a. obtaining a biological sample from the patient; and

b. detecting the presence or absence of at least one epithelial cancer biomarker in the biological sample,

wherein the presence of at least one epithelial cancer biomarker is indicative of cancer of epithelial origin, and wherein the epithelial cancer biomarker is selected from the group consisting of Cystatin B, Chaperonin 10, and Profilin.

3. The method of claim 1 or 2, wherein the cancer of epithelial origin is selected from the group consisting of breast cancer, basal cell carcinoma, adenocarcinoma, gastrointestinal cancer, lip cancer, mouth cancer, esophageal cancer, small bowel cancer, stomach cancer, colon cancer, liver cancer, bladder cancer, pancreas cancer, ovary cancer, cervical cancer, lung cancer, skin cancer, prostate cancer, and renal cell carcinoma.

7. The method of claim 1, 2, 4, 5, or 6 wherein the biological sample is urine.

8. The method of claim 1 or 4 wherein the presence or absence of at least one epithelial cancer biomarker or Cystatin B is detected using an antibody-based binding moiety which specifically binds to at least one epithelial cancer biomarker or to Cystatin B.

9. The method according to claim 8 wherein the antibody-based binding moiety is labeled with a detectable label.

10. The method according to claim 9 wherein the label is selected from the group consisting of a radioactive label, a hapten label, a fluorescent label, and an enzymatic label.

11. The method according to claim 8 wherein the antibody-based binding moiety is an antibody.

12. The method according to claim 11, wherein the antibody is an monoclonal antibody.

2. A method for diagnosing a cancer of epithelial origin in a patient comprising:

a. measuring at least one epithelial cancer biomarker levels present in a biological sample obtained from the patient, a test sample;

b. comparing the level of at least one epithelial cancer biomarker in the test sample with the level of epithelial cancer biomarker present in a control sample;

wherein a higher level of at least one epithelial cancer biomarker in the test sample as compared to the level of epithelial cancer biomarker in the control sample is indicative of cancer of epithelial origin, and wherein the epithelial cancer biomarker is selected from the group consisting of Cystatin B, Chaperonin 10, and Profilin.

13. The method of any of claims 2, 5 or 6 wherein the level of at least one epithelial cancer biomarker or Cystatin B is measured by measuring the protein level of at least one epithelial cancer biomarker protein or Cystatin B.

14. The method of claim 13 wherein the protein level of epithelial cancer biomarker or level of Cystatin B is measured by a method comprising the steps of:

a. contacting the test sample, or preparation thereof, with an antibody-based binding moiety which specifically binds the epithelial cancer biomarker or to Cystatin B to form an antibody-epithelial cancer biomarker complex; and

b. detecting the presence of the complex, thereby measuring the level of epithelial cancer biomarker present.

15. The method according to claim 14 wherein the antibody-based binding moiety is labeled with a detectable label.

16. The method according to claim 15 wherein the label is selected from the group consisting of a radioactive label, a hapten label, a fluorescent label, and an enzymatic label.

17. The method according to claim 14 wherein the antibody-based binding moiety is an antibody.

18. The method according to claim 17 wherein the antibody is an monoclonal antibody.

4. A method for facilitating the diagnosis of bladder cancer in a patient comprising:

a. obtaining a biological sample from the patient; and

b. detecting the presence or absence of Cystatin B in the biological sample, wherein the presence of Cystatin B epithelial cancer biomarker is indicative of bladder cancer.

5. A method for diagnosing bladder cancer in a patient comprising:

a. measuring the levels of Cystatin B present in a biological sample obtained from the patient, a test sample;

b. comparing the level of Cystatin B in the test sample with the level of Cystatin B epithelial cancer biomarker present in a control sample;

wherein a higher level Cystatin B in the test sample as compared to the level of Cystatin B in the control sample is indicative of bladder cancer.

6. A method for diagnosing invasive bladder cancer in a patient comprising:

a. measuring the levels of Cystatin B present in a biological sample obtained from the patient, a test sample;

b. comparing the level of Cystatin B in the test sample with the level of Cystatin B present in a non-invasive control sample;

wherein a higher level Cystatin B in the test sample as compared to the level of Cystatin B in the non-invasive control sample is indicative of invasive bladder cancer.

19. A kit for detecting at least one epithelial cancer biomarker in a urine sample comprising a container for holding a urine sample, and at least one antibody that specifically binds an epithelial cancer biomarker.

20. The kit of claim 19 wherein the kit comprises two antibodies that specifically bind to at least one epithelial cancer biomarker, one antibody is immobilized on a solid phase and one antibody is detectably labeled.

23. The kit of claim 19 or 21, further comprising directions for use.

21. A kit for detecting Cystatin B in a urine sample comprising a container for holding a urine sample, and at least one antibody that specifically binds Cystatin B.

22. The kit of claim 21 wherein the kit comprises two antibodies that specifically bind to Cystatin B, one antibody is immobilized on a solid phase and one antibody is detectably labeled.

24. A method for assessment of a cancer of epithelial origin, the method comprising:

(a) assaying for cystatin B in a sample obtained from a subject; and

(b) determining whether cystatin B is present at a level higher than a predetermined level,

thereby indicating whether the subject is at an increased risk of cancer progression.

25. The method of claim 24 wherein the sample is selected from the group consisting of a urine, blood, serum, plasma, stool, sputum, cerebrospinal fluid, nipple aspirate, and tissue sample.

26. The method of claim 24 wherein the sample is a urine sample.

27. The method of claim 24 wherein the cancer of epithelial origin is selected from the group consisting of bladder cancer, breast cancer, basal cell carcinoma, adenocarcinoma, gastrointestinal cancer, lip cancer, mouth cancer, esophageal cancer, small bowel cancer, stomach cancer, colon cancer, liver cancer, pancreas cancer, ovary cancer, cervical cancer, lung cancer, skin cancer, prostate cancer, and renal cell carcinoma.

28. The method of claim 24 wherein the cancer of epithelial origin is bladder cancer.

29. The method of claim 24 wherein the predetermined level is based on the level of cystatin B normally found in biological samples of healthy subjects.

30. The method of claim 24 wherein the predetermined level is based on a prior measurement of the subject'"'"'s cystatin B level.

31. The method of claim 24 wherein the predetermined level is based on the subject'"'"'s cystatin B level prior to treatment.

32. The method of claim 24 wherein the subject'"'"'s cystatin B level is monitored over time.

33. The method of claim 24 wherein the cancer progression is a recurrence of cancer.

34. The method of claim 24 wherein the cancer progression is an increase of metastatic activity.

35. The method of claim 24 wherein the cancer progression is a progression in cancer grade or stage.

36. The method of claim 24 wherein cystatin B protein is assayed.

37. The method of claim 36 wherein the cystatin B protein is assayed for by an immunoassay or by mass spectrometry.