Use of markers in the diagnosis and treatment of prostate cancer

• US 9,797,905 B2
• Filed: 03/02/2016
• Issued: 10/24/2017
• Est. Priority Date: 06/27/2012
• Status: Active Grant

• Current Assignee: BPGbio Inc
• Original Assignee: Berg LLC (BPGbio Inc)
• Inventors: Narain, Niven Rajin, Sarangarajan, Rangaprasad, Vishnudas, Vivek K.
• Primary Examiner(s): AEDER, SEAN E
• Application Number:
  US15/059,238
• Publication Number:
  US 20160178632A1
• Time in Patent Office: 601 Days
• Field of Search: None
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2333/47 Assays involving proteins of known structure or function as defined in the subgroups
• CPC Class Codes: G01N 2333/4742 Keratin; Cytokeratin
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• CPC Class Codes: G01N 2800/56 Staging of a disease; Further complications associated with the disease
• CPC Class Codes: G01N 33/57434 of prostate
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

The invention provides method for diagnosis, monitoring, and prognosis of prostate cancer using one or more of keratin 4, keratin 7, keratin 8, keratin 15, keratin 18, keratin 19, tubulin-beta 3, filamin B, and LY9, and PSA. The invention provides kits for practicing the methods of the invention.

Claims

1. A method for diagnosing and treating prostate cancer in a subject comprising:

(1) detecting the protein level of one or more of the prostate cancer related markers filamin B and keratin 19 in a serum sample isolated from a subject suspected of having prostate cancer;

(2) comparing the protein level of the one or more prostate cancer related markers in the serum sample with the protein level of the one or more prostate cancer related markers in a normal control sample;

(3) diagnosing the subject as having prostate cancer when an increased protein level of the one or more prostate cancer related markers is detected in the serum sample relative to the normal control sample; and

(4) performing surgical prostate resection on the diagnosed subject, thereby diagnosing and treating prostate cancer in the subject.

2. The method of claim 1, wherein detecting the level of one or more of the prostate cancer related markers filamin B and keratin 19 comprises contacting the sample with one or more reagents that selectively bind at least one of filamin B and keratin 19.

3. The method of claim 2, wherein the one or more reagent is an antibody.

4. The method of claim 1, wherein the prostate cancer related marker is filamin B.

5. The method of claim 1, wherein the prostate cancer related marker is keratin 19.

6. The method of claim 1, wherein no increase in one or more of filamin B and keratin 19 in the biological sample relative to the normal control sample is indicative of a normal prostate state in the subject.

7. The method of claim 1, further comprising detecting the level of prostate specific antigen (PSA) in the sample.

8. The method of claim 7, further comprising comparing the level of PSA in the sample to the level of PSA in a normal control sample.

9. The method of claim 8, wherein an increase in the detected level of one or more of filamin B and keratin 19 in the sample relative to the normal control sample, in combination with an increase in the level of PSA in the sample relative to the level of PSA in the normal control sample, is indicative of prostate cancer in the subject.

10. The method of claim 8, wherein no increase in the detected level of one or more of filamin B and keratin 19 in the sample relative to the normal control sample, in combination with a decreased or normal level of PSA in the sample as compared to the level of PSA in the normal control sample, is indicative of a normal prostate state in the subject.

11. The method of claim 1, wherein prior to step (1), the subject has been determined to be at an increased risk of prostate cancer.

12. The method of claim 11, wherein the increased risk for prostate cancer is due to increased age.

13. A method for diagnosing and treating prostate cancer in a subject comprising:

(1) detecting the protein level of the prostate cancer related marker filamin B in a serum sample isolated from a subject suspected of having prostate cancer;

(2) comparing the protein level of filamin B in the serum sample with the protein level of filamin B in a normal control sample;

(3) diagnosing the subject as having prostate cancer when an increased protein level of filamin B is detected in the serum sample relative to the normal control sample; and

(4) performing surgical resection on the diagnosed subject, thereby diagnosing and treating prostate cancer in the subject.

14. The method of claim 13, wherein detecting the level of filamin B comprises contacting the sample with one or more reagents that selectively bind filamin B.

15. The method of claim 14, wherein the one or more reagent is an antibody.

16. The method of claim 13, wherein no increase in filamin B in the biological sample relative to the normal control sample is indicative of a normal prostate state in the subject.

17. The method of claim 13, further comprising detecting the level of prostate specific antigen (PSA) in the sample.

18. The method of claim 17, further comprising comparing the level of PSA in the sample to the level of PSA in a normal control sample.

19. The method of claim 18, wherein an increase in the detected level of filamin B in the sample relative to the normal control sample, in combination with an increase in the level of PSA in the sample relative to the level of PSA in the normal control sample, is indicative of prostate cancer in the subject.

20. The method of claim 18, wherein no increase in the detected level of filamin B in the sample relative to the normal control sample, in combination with a decreased or normal level of PSA in the sample as compared to the level of PSA in the normal control sample, is indicative of a normal prostate state in the subject.

21. The method of claim 13, wherein prior to step (1), the subject has been determined to be at an increased risk of prostate cancer.

22. The method of claim 21, wherein the increased risk is due to increased age.

30. The method of claim 21, wherein an increase in the detected level of filamin B in the sample relative to the normal control sample, in combination with an increase in the level of PSA in the sample relative to the level of PSA in the normal control sample, is indicative of prostate cancer in the subject.

31. The method of claim 21, wherein no increase in the detected level of filamin B in the sample relative to the normal control sample, in combination with a decreased or normal level of PSA in the sample as compared to the level of PSA in the normal control sample, is indicative of a normal prostate state in the subject.

23. A method for diagnosing and treating prostate cancer in a subject comprising:

(1) detecting the protein level of the prostate cancer related marker filamin B in a serum sample isolated from a subject suspected of having prostate cancer;

(2) comparing the protein level of filamin B in the serum sample with the protein level of filamin B in a normal control sample;

(3) diagnosing the subject as having prostate cancer when an increased protein level of filamin B is detected in the serum sample relative to the normal control sample; and

(4) administering radiation therapy to the diagnosed subject, thereby diagnosing and treating prostate cancer in the subject.

24. The method of claim 23, wherein the radiation therapy is brachytherapy.

25. The method of claim 23, wherein detecting the level of filamin B comprises contacting the sample with one or more reagents that selectively bind filamin B.

26. The method of claim 25, wherein the one or more reagent is an antibody.

27. The method of claim 23, wherein no increase in filamin B in the biological sample relative to the normal control sample is indicative of a normal prostate state in the subject.

28. The method of claim 23, further comprising detecting the level of prostate specific antigen (PSA) in the sample.

29. The method of claim 28, further comprising comparing the level of PSA in the sample to the level of PSA in a normal control sample.

32. The method of claim 23, wherein prior to step (1), the subject has been determined to be at an increased risk of prostate cancer.

33. The method of claim 24, wherein the increased risk is due to increased age.