Compositions and methods for detecting and treating prostate carcinoma

Abstract

Compositions and methods for the diagnosis, treatment and prevention of prostate cancer, as well as for treatment selection.

1 . A method for identifying a neoplasia in a subject, the method comprising identifying an increased level of a Marker nucleic acid molecule or polypeptide selected from the group consisting of OCT3/4, Nanog, Sox2, c-Myc, Klf4, Keratin 8, and uPAR in a biological sample derived from the subject, relative to the level present in a reference, thereby identifying a neoplasia in the subject. 
     
     
         2 . The method of  claim 1 , wherein the neoplasia is prostate carcinoma in the subject. 
     
     
         3 . The method of  claim 1 , wherein the identification of increased levels of OCT3/4, Nanog, and Sox2 nucleic acid molecules or polypeptides in a biological sample derived from the subject, relative to the levels present in a reference, identifies a neoplasia in the subject. 
     
     
         4 . The method of  claim 1 , further comprising identifying an increase in c-Myc nucleic acid molecules or polypeptides in a biological sample derived from the subject, relative to the level present in a reference, thereby identifying a neoplasia in the subject. 
     
     
         5 . The method of  claim 1 , wherein the Marker is Sox2. 
     
     
         6 . The method of  claim 1 , further comprising identifying an increase in E-cadherin nucleic acid molecules or polypeptides in a biological sample derived from the subject, relative to the level present in a reference, thereby identifying a neoplasia or prostate carcinoma in the subject. 
     
     
         7 . The method of  claim 1 , wherein the biological sample is a tissue sample or biopsy sample. 
     
     
         8 . The method of  claim 1 , wherein the biological sample is a biological fluid selected from the group consisting of blood, blood serum, plasma, saliva, urine, seminal fluid, and ejaculate. 
     
     
         9 . The method of  claim 1 , wherein an increase in the level of one or more of said Markers distinguishes prostate carcinoma from benign prostatic hyperplasia. 
     
     
         10 . A method for diagnosing the presence or absence of neoplasia in a subject, the method comprising detecting the level of OCT3/4, Nanog, and Sox2 Marker polypeptides or nucleic acid molecules in blood of a subject, relative to the level present in a reference, wherein detection of an increase in said Markers diagnoses the subject as having neoplasia, and failure to detect said Markers diagnoses the subject as not having neoplasia. 
     
     
         11 . The method of  claim 1 , where the neoplasia is prostate cancer. 
     
     
         12 . The method of  claim 10 , further comprising detecting a c-Myc nucleic acid molecule or polypeptide in blood of the subject, relative to the level present in a reference, wherein an increased level of c-Myc identifies the subject as having neoplasia or prostate cancer. 
     
     
         13 . (canceled) 
     
     
         14 . A method for identifying a prostate carcinoma in a subject, the method comprising
 a) isolating cells that bind an E-cadherin capture reagent from a biological sample derived from a subject; and   b) analysing said cells for a Marker nucleic acid molecule or polypeptide selected from the group consisting of OCT3/4, Nanog, Sox2, c-Myc, Klf4, Keratin 8, and uPAR, wherein an increased level of said Marker relative to the level present in a reference, identifies a prostate carcinoma in the subject.   
     
     
         15 - 16 . (canceled) 
     
     
         17 . A method for characterizing the aggressiveness of a prostate cancer in a subject, the method comprising comparing the level of a one or more nucleic acid molecules or polypeptide Markers selected from the group consisting of OCT3/4, Nanog, Sox2, c-Myc, Klf4, Keratin 8, and uPAR in a biological sample of the subject, relative to the level present in a reference, wherein an increase in the level of one or more of said Markers identifies the prostate cancer as aggressive and the absence of an increase identifies the prostate cancer as less aggressive. 
     
     
         18 - 22 . (canceled) 
     
     
         23 . The method of  claim 17 , wherein an increase in the level of one or more of said Markers identifies the prostate cancer as metastatic or as having a propensity to metastasize. 
     
     
         24 - 33 . (canceled) 
     
     
         34 . The method of  claim 17 , wherein an increase in the level of one or more of said Markers identifies the subject as having a poor prognosis. 
     
     
         35 - 38 . (canceled) 
     
     
         39 . A method of monitoring prostate cancer therapy in a subject, the method comprising determining the level of a Marker selected from the group consisting of OCT3/4, Nanog, Sox2, c-Myc, Klf4, Keratin 8, and uPAR nucleic acid molecule or polypeptide in a biological sample derived from the subject, relative to the level present in a reference, wherein a prostate cancer therapy that reduces the level of said marker is identified as effective. 
     
     
         40 - 44 . (canceled) 
     
     
         45 . A method of selecting a treatment for a subject diagnosed as having prostate cancer, the method comprising:
 (a) detecting the presence or absence of one or more markers selected from the group consisting of OCT3/4, Nanog, Sox2, c-Myc, Klf4, Keratin 8, and uPAR in a biologic sample from the subject; and   (b) selecting a treatment from the group consisting of surveillance, surgery, hormone therapy, chemotherapy, and radiotherapy.   
     
     
         46 - 49 . (canceled) 
     
     
         50 . The method of  claim 1 , wherein the biological sample is a tissue sample selected from the list consisting of prostate tissue and peripheral blood mononuclear cells (PBMC) or wherein the biological sample is a biological fluid selected from the group consisting of blood, blood serum, plasma, saliva, urine, seminal fluids, and ejaculate. 
     
     
         51 - 61 . (canceled) 
     
     
         62 . A kit for the analysis of OCT3/4, Nanog, Sox2, c-Myc, Klf4, Keratin 8, and uPAR, the kit comprising at least one agent capable of specifically binding or hybridizing to an OCT3/4, Nanog, Sox2, c-Myc, Klf4, Keratin 8, and uPARpolypeptide or nucleic acid molecule Markers, and directions for using the agent for the analysis of OCT3/4, Nanog, Sox2, c-Myc or Klf4 Markers. 
     
     
         63 - 68 . (canceled) 
     
     
         69 . A microarray comprising Markers bound to a solid support, wherein the Markers are selected from the group consisting of OCT3/4, Nanog, Sox2, c-Myc, Klf4, Keratin 8, and uPAR polypeptides or nucleic acid molecules, or fragments thereof. 
     
     
         70 - 71 . (canceled)