Use of markers in the diagnosis and treatment of prostate cancer

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.

1 . A method for diagnosing an abnormal prostate state in a subject comprising:
 (1) determining a level of one or more prostate cancer related markers selected from the group consisting of filamin B, LY9, keratin 4, keratin 7, keratin 8, keratin 15, keratin 18, keratin 19, and tubulin-beta 3 in a biological sample from the subject; and   (2) comparing the level of the one or more prostate cancer related markers in the biological sample with the level of the one or more prostate cancer related markers in a normal control sample, wherein an altered level of the one or more prostate cancer related markers in the biological sample relative to the normal control sample is indicative of an abnormal prostate state in the subject.   
     
     
         2 . The method of  claim 1 , wherein the one or more prostate cancer related markers is selected from the group consisting of filamin B, LY9, and keratin 19. 
     
     
         3 . The method of  claim 1 , wherein an increased level of one or more prostate cancer related markers selected from the group consisting of filamin B, LY9, and keratin 19 in the biological sample relative to the normal control sample is indicative of an abnormal prostate state in the subject. 
     
     
         4 . The method of  claim 1 , wherein no increase in the detected level of each of the one or more prostate-cancer related markers selected from the group consisting of filamin B, LY9, and keratin 19 in the biological sample relative to the normal control sample is indicative of a normal prostate state in the subject. 
     
     
         5 . The method of  claim 1 , further comprising detecting the level of prostate specific antigen (PSA) in the biological sample. 
     
     
         6 . The method of  claim 5 , further comprising comparing the level of PSA in the biological sample to the level of PSA in a normal control sample. 
     
     
         7 . The method of  claim 6 , wherein an increase in the level of one or more prostate cancer related markers selected from the group consisting of filamin B, LY9, and keratin 19 in the biological sample relative to the normal control sample, in combination with an increase in the level of PSA in the biological sample relative to the level of PSA in the normal control sample is indicative of an abnormal prostate state in the subject. 
     
     
         8 . The method of  claim 7 , wherein no increase in the detected level of expression of each of the one or more prostate-cancer related markers selected from the group consisting of filamin B, LY9, and keratin 19 in the biological sample relative to the normal control sample, in combination with a decreased or normal level of PSA in the biological sample as compared to the level of PSA in the normal control sample, is indicative of a normal prostate state in the subject. 
     
     
         9 . The method of  claim 2 , wherein the one or more prostate cancer markers selected from the group consisting of filamin B, LY9 and keratin 19 is: filamin B; LY9; keratin 19; filamin B and LY9; filamin B and keratin 19; LY9 and keratin 19; or filamin B, LY9, and keratin 19. 
     
     
         10 . The method of  claim 1 , wherein the abnormal prostate state is prostate cancer. 
     
     
         11 - 15 . (canceled) 
     
     
         16 . A method for identifying a subject as being at increased risk for developing prostate cancer, the method comprising:
 (1) determining a level of one or more prostate cancer related markers selected from the group consisting of filamin B, LY9, keratin 4, keratin 7, keratin 8, keratin 15, keratin 18, keratin 19, and tubulin-beta 3 in a biological sample from the subject; and   (2) comparing the level of the one or more prostate cancer related markers in the biological sample with the level of the one or more prostate cancer related markers in a normal control sample, wherein an altered level of the one or more prostate cancer related markers in the biological sample relative to the normal control sample is indicative of an increased risk for developing prostate cancer in the subject.   
     
     
         17 . The method of  claim 16 , wherein the one or more prostate cancer related markers is selected from the group consisting of filamin B, LY9, and keratin 19. 
     
     
         18 - 37 . (canceled) 
     
     
         38 . A method for monitoring prostate cancer in a subject, the method comprising
 (1) determining a level of one or more prostate cancer related markers selected from the group consisting of filamin B, LY9, keratin 4, keratin 7, keratin 8, keratin 15, keratin 18, keratin 19, and tubulin-beta 3 in a first biological sample obtained at a first time from a subject having prostate cancer;   (2) determining a level of expression of the one or more prostate cancer related markers in a second biological sample obtained from the subject at a second time, wherein the second time is later than the first time; and   (3) comparing the level of the one or more prostate cancer related markers in the second sample with the level of the one or more prostate cancer related markers in the first sample, wherein a change in the level of the one or more prostate cancer related markers in the second sample as compared to the first sample is indicative of a change in prostate cancer status in the subject.   
     
     
         39 . The method of  claim 38 , wherein the subject is actively treated for prostate cancer prior to obtaining the second sample. 
     
     
         40 . The method of  claim 38 , wherein the subject is not actively treated for prostate cancer prior to obtaining the second sample. 
     
     
         41 . The method of  claim 38 , wherein the one or more prostate cancer related markers is selected from the group consisting of filamin B, LY9, and keratin 19. 
     
     
         42 . The method of  claim 38 , wherein an increased level of one or more prostate cancer related markers selected from the group consisting of filamin B, LY9, and keratin 19 in the second biological sample as compared to the first biological sample is indicative of progression of the prostate cancer in the subject. 
     
     
         43 . The method of  claim 38 , wherein no increase in the detected level of expression of each of the one or more prostate-cancer related markers selected from the group consisting of filamin B, LY9, and keratin 19 in the second biological sample as compared to the first biological sample is indicative of non-progression of the prostate cancer in the subject. 
     
     
         44 . The method of  claim 38 , further comprising determining the level of prostate specific antigen (PSA) in the first biological sample and the second biological sample. 
     
     
         45 . The method of  claim 44 , further comprising comparing the level of PSA in the second biological sample to the level of PSA in the first biological sample. 
     
     
         46 - 61 . (canceled) 
     
     
         62 . A method for detecting a set of prostate cancer related markers, the method comprising:
 (1) analyzing a biological sample from a subject for a level of two or more prostate cancer related markers of a set of prostate cancer related markers, wherein the set of prostate cancer related markers comprises filamin B, LY9, keratin 4, keratin 7, keratin 8, keratin 15, keratin 18, keratin 19, and tubulin-beta 3;   (2) detecting each of the two or more prostate specific makers in the biological sample, thereby detecting the set of prostate cancer related biomarkers.   
     
     
         63 . The method of  claim 62 , wherein the set of prostate cancer related markers comprises filamin B, LY9, and keratin 19. 
     
     
         64 . The method of  claim 63 , wherein the two or more prostate cancer related markers of the set of prostate cancer related markers is: filamin B and LY9; filamin B and keratin 19; LY9 and keratin 19; or filamin B, LY9, and keratin 19. 
     
     
         65 . The method of  claim 62 , wherein the set of prostate cancer related markers comprises keratin 4, keratin 7, keratin 8, keratin 15, keratin 18, and tubulin beta-3. 
     
     
         66 . The method of  claim 62 , wherein the set of prostate cancer related markers comprises keratin 7, keratin 8, and keratin 15. 
     
     
         67 . The method of  claim 62 , wherein the set of prostate cancer related markers comprises keratin 7 and keratin 15. 
     
     
         68 - 75 . (canceled) 
     
     
         76 . A panel of reagents for use in a detection method, the panel comprising at least two detection reagents, wherein each detection reagent is specific for the detection of at least one prostate cancer related marker of a set of prostate cancer related markers, wherein the set of prostate cancer specific markers comprises two or more prostate cancer related markers selected from the group consisting of filamin B, LY9, keratin 4, keratin 7, keratin 8, keratin 15, keratin 18, keratin 19, tubulin-beta 3 and PSA. 
     
     
         77 . The panel of  claim 76 , wherein the set of prostate cancer specific markers comprises two or more prostate cancer related markers selected from the group consisting of filamin B, LY9, and keratin 19. 
     
     
         78 . The panel of  claim 77 , wherein the two or more prostate cancer related markers is: filamin B and LY9; filamin B and keratin 19; LY9 and keratin 19; or filamin B, LY9, and keratin 19. 
     
     
         79 . The panel of  claim 76 , wherein the set of prostate cancer specific markers comprises two or more prostate cancer related markers selected from the group consisting of keratin 4, keratin 7, keratin 8, keratin 15, keratin 18, and tubulin beta-3. 
     
     
         80 . The panel of  claim 76 , wherein the set of prostate cancer specific markers comprises two or more prostate cancer related markers selected from the group consisting of keratin 7, keratin 8, and keratin 15. 
     
     
         81 . The panel of  claim 76 , wherein the set of prostate cancer specific markers comprises keratin 7 and keratin 15. 
     
     
         82 . The panel of  claim 76 , wherein the set of prostate cancer specific markers further comprises PSA. 
     
     
         83 . The panel of  claim 82 , wherein the panel of reagents comprises a detection reagent specific for the detection of PSA. 
     
     
         84 . (canceled) 
     
     
         85 . A kit for the diagnosis, monitoring, or characterization of an abnormal prostate state, comprising:
 at least one reagent specific for the detection of a level of at least one prostate cancer related marker selected from the group consisting of keratin 4, keratin 7, keratin 8, keratin 15, keratin 18, keratin 19, and tubulin-beta 3, filamin B, and LY9.   
     
     
         86 . The kit of  claim 85 , wherein the kit further comprises instructions for the diagnosis, monitoring, or characterization of an abnormal prostate state based on the level of the at least one prostate cancer related marker selected from the group consisting of keratin 4, keratin 7, keratin 8, keratin 15, keratin 18, keratin 19, and tubulin-beta 3, filamin B, and LY9 detected. 
     
     
         87 . The kit of  claim 85 , wherein the kit further comprises instructions to detect the level of PSA in a sample in which the at least one prostate cancer related marker selected from the group consisting of keratin 4, keratin 7, keratin 8, keratin 15, keratin 18, keratin 19, and tubulin-beta 3, filamin B, and LY9 is detected. 
     
     
         88 . The kit of  claim 85 , further comprising at least one reagent specific for the detection of a level of PSA. 
     
     
         89 . A kit comprising at least one reagent specific for the detection of a level of at least one prostate cancer related marker selected from the group consisting of keratin 4, keratin 7, keratin 8, keratin 15, keratin 18, keratin 19, tubulin-beta 3, filamin B, and LY9 and at least one reagent specific for the detection of a level of PSA.