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) isolating a serum sample or a plasma sample from a subject having or suspected of having an abnormal prostate state and detecting the level of one or more of the prostate cancer related markers filamin B and keratin 19 in the serum sample or plasma sample; 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 detecting the level of one or more of the prostate cancer related markers filamin B and keratin 19 comprises contacting the biological 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 an increased level of one or more of filamin B and keratin 19 in the biological sample relative to the normal control sample is indicative of an abnormal prostate state in the subject. 
     
     
         7 . 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. 
     
     
         8 . The method of  claim 1 , further comprising detecting the level of prostate specific antigen (PSA) in the biological sample. 
     
     
         9 . The method of  claim 8 , further comprising comparing the level of PSA in the biological sample to the level of PSA in a normal control sample. 
     
     
         10 . The method of  claim 9 , wherein an increase in the detected level of one or more of filamin B 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. 
     
     
         11 . The method of  claim 10 , wherein no increase in the detected level of one or more of filamin B 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. 
     
     
         12 . The method of  claim 1 , wherein the abnormal prostate state is prostate cancer. 
     
     
         13 . A method for identifying a subject as being at increased risk for developing prostate cancer, the method comprising:
 (1) isolating a serum sample or a plasma sample from a subject having or suspected of having an abnormal prostate state, and detecting the level of one or more of prostate cancer related markers filamin B and keratin 19 in the serum sample or plasma sample; 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.   
     
     
         14 . The method of  claim 13 , wherein detecting the level of one or more of the prostate cancer related markers filamin B and keratin 19 comprises contacting the biological sample with one or more reagents that selectively bind at least one of filamin B and keratin 19. 
     
     
         15 . The method of  claim 14 , wherein the one or more reagent is an antibody. 
     
     
         16 . The method of  claim 13 , wherein the prostate cancer related marker is filamin B. 
     
     
         17 . The method of  claim 13 , wherein the prostate cancer related marker is keratin 19. 
     
     
         18 . A method for monitoring prostate cancer in a subject, the method comprising
 (1) isolating a first biological sample obtained at a first time from a subject having prostate cancer and detecting the level of one or more prostate cancer related markers selected from the group consisting of filamin B and keratin 19 in the first biological sample;   (2) isolating a second biological sample obtained at a second time from a subject having prostate cancer and detecting the level of the one or more prostate cancer related markers selected from the group consisting of filamin B and keratin 19 in the 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.   
     
     
         19 . The method of  claim 18 , wherein detecting the level of one or more of the prostate cancer related markers filamin B and keratin 19 comprises contacting the biological sample with one or more reagents that selectively bind at least one of filamin B and keratin 19. 
     
     
         20 . The method of  claim 19 , wherein the one or more reagent is an antibody. 
     
     
         21 . The method of  claim 18 , wherein the subject is actively treated for prostate cancer prior to obtaining the second sample. 
     
     
         22 . The method of  claim 18 , wherein the subject is not actively treated for prostate cancer prior to obtaining the second sample. 
     
     
         23 . The method of  claim 18 , wherein the prostate cancer related marker is filamin B. 
     
     
         24 . The method of  claim 18 , wherein the prostate cancer related marker is keratin 19. 
     
     
         25 . The method of  claim 18 , wherein an increase in the detected level of one or more of filamin B 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. 
     
     
         26 . The method of  claim 18 , wherein no increase in the detected level of one or more of filamin B 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. 
     
     
         27 . The method of  claim 18 , further comprising determining the level of prostate specific antigen (PSA) in the first biological sample and the second biological sample. 
     
     
         28 . The method of  claim 27 , further comprising comparing the level of PSA in the second biological sample to the level of PSA in the first biological sample.