Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of prostate cancer

Abstract

Novel markers for prostate cancer that are both sensitive and accurate. Furthermore, these markers are able to distinguish between prostate cancer and benign prostate hyperplasia (“BPH”). These markers are overexpressed in prostate cancer specifically, as opposed to normal prostate tissue and/or BPH. The measurement of these markers, alone or in combination, in patient samples provides information that the diagnostician can correlate with a probable diagnosis of prostate cancer. The markers of the present invention, alone or in combination, show a high degree of differential detection between prostate cancer and non-cancerous states.

1 . An isolated polynucleotide comprising the polynucleotide sequence set forth in a member selected from the group consisting of 5, 6, 7, 8, 9, 10, 34, 35, 36, 37, 38, 39, 13, 14, 435, 436, 437-450 and 451.  
     
     
         2 . An isolated polynucleotide, comprising the polynucleotide sequence set forth in a member selected from the group consisting of 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 136, 137, 138, 139, 140, 141, 142, 422, 423, 424-433 and 434.  
     
     
         3 . An isolated polypeptide comprising the polypeptide sequence set forth in a member selected from the group consisting of 331, 332, 333, 334, 335, 359, 360, 361, 362, 363, 338, 339, 452, 453-462 and 463.  
     
     
         4 . An isolated polypeptide, comprising the polypeptide selected from the group consisting of: 
 a polypeptide comprising a first amino acid sequence being at least about 95% homologous to amino acids 1-63 of SEQ ID NO:334, and a second amino acid sequence being at least about 95% homologous to amino acids 64-84 of SEQ ID NO:334, wherein said first and second amino acid sequences are contiguous and in a sequential order;    a polypeptide comprising a first amino acid sequence being at least 95% homologous to amino acids 1-163 of SEQ ID NO. 359, a bridging amino acid H corresponding to amino acid 164 of SEQ ID NO. 359, a second amino acid sequence being at least 95% homologous to amino acids 165-445 of SEQ ID NO. 359, and a third amino acid sequence being at least about 95% homologous to amino acids 446-496 of SEQ ID NO. 359, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order;    a polypeptide comprising a first amino acid sequence being at least about 95% homologous to amino acids 1-163 of SEQ ID NO:360, a bridging amino acid H corresponding to amino acid 164 of SEQ ID NO. 360, a second amino acid sequence being at least about 95% homologous to amino acids 165-358 of SEQ ID NO. 360, and a third amino acid sequence being at least about 95% homologous to amino acids 359-382 of SEQ ID NO. 360, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order;    a polypeptide comprising a first amino acid sequence being at least about 95% homologous to amino acids 1-163 of SEQ ID NO. 361, a bridging amino acid H corresponding to amino acid 164 of SEQ ID NO. 361, a second amino acid sequence being at least about 95% homologous to amino acids 165-359 of SEQ ID NO. 361, and a third amino acid sequence being at least about 95% homologous to amino acids 360-370 of SEQ ID NO. 361, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order;    a polypeptide comprising a first amino acid sequence being at least about 95% homologous to amino acids 1-163 of SEQ ID NO. 362, a bridging amino acid H corresponding to amino acid 164 of SEQ ID NO. 362, a second amino acid sequence being at least about 95% homologous to amino acids 165-286 of SEQ ID NO. 362, and a third amino acid sequence being at least about 95% homologous to amino acids 287-301 of SEQ ID NO. 362, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order;    a polypeptide comprising a first amino acid sequence being at least about 95% homologous to amino acids 1-96 of SEQ ID NO. 363, a second amino acid sequence being at least about 95% homologous to amino acids 97-147 of SEQ ID NO. 363, a bridging amino acid H corresponding to amino acid 148 of SEQ ID NO. 363, a third amino acid sequence being at least about 95% homologous to amino acids 149-343 of SEQ ID NO. 363, and a fourth amino acid sequence being at least about 95% homologous to amino acids 344-354 of SEQ ID NO. 363, wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order;    a polypeptide comprising a first amino acid sequence being at least about 95% homologous to amino acids 1-27 of SEQ ID NO. 339, and a second amino acid sequence being at least about 95% homologous to amino acids 28-41 of SEQ ID NO. 339, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order;    a polypeptide comprising a first amino acid sequence being at least about 95% homologous to amino acids 1-110 of SEQ ID NO. 332, and a second amino acid sequence being at least about 95% homologous to amino acids 111-222 of SEQ ID NO. 332, wherein said first and second amino acid sequences are contiguous and in a sequential order;    a polypeptide comprising a first amino acid sequence being at least about 95% homologous to amino acids 1-5 of SEQ ID NO. 333, a second amino acid sequence being at least about 95% homologous to amino acids 6-64 of SEQ ID NO. 333, and a third amino acid sequence being at least about 95% homologous to amino acids 65-93 of SEQ ID NO. 333, wherein said first, second and third amino acid sequences are contiguous and in a sequential order;    a polypeptide comprising a first amino acid sequence being at least about 95% homologous to amino acids 1-63 of SEQ ID NO. 334, and a second amino acid sequence being at least about 95% homologous to amino acids 64-84 of SEQ ID NO. 334, wherein said first and second amino acid sequences are contiguous and in a sequential order; and    a polypeptide comprising a first amino acid sequence being at least about 95% homologous to amino acids 1-63 of SEQ ID NO. 335, and a second amino acid sequence being at least about 95% homologous to a polypeptide sequence corresponding to amino acids 64-90 of SEQ ID NO. 335, wherein said first and second amino acid sequences are contiguous and in a sequential order.    
     
     
         5 . The isolated polypeptide of  claim 4 , comprising a member selected from the group consisting of 
 a polypeptide comprising an amino acid sequence being at least about 95% about homologous to SEQ ID NO: 538;    a polypeptide comprising an amino acid sequence being at least about 95% about homologous to amino acids 446-496 in SEQ ID NO. 359;    a polypeptide comprising an amino acid sequence being at least about 95% about homologous to amino acids 359-382 in SEQ ID NO. 360;    a polypeptide comprising an amino acid sequence being at least about 95% homologous to amino acids 360-370 in SEQ ID NO. 361;    a polypeptide comprising an amino acid sequence being at least about 95% homologous to amino acids 287-301 in SEQ ID NO. 362;    a polypeptide comprising an amino acid sequence being at least about 95% homologous to the sequence in SEQ ID NO. 363;    a polypeptide comprising an amino acid sequence being at least about 95% homologous to amino acids 28-41 in SEQ ID NO. 339;    a polypeptide comprising an amino acid sequence being at least about 95% homologous to amino acids 84-222 in SEQ ID NO. 332;    a polypeptide comprising an amino acid sequence being at least about 95% homologous to amino acids 65-93 in SEQ ID NO. 333;    a polypeptide comprising an amino acid sequence being at least about 95% homologous to amino acids 64-84 in SEQ ID NO. 334;    a polypeptide comprising an amino acid sequence being at least about 95% homologous to amino acids 64-90 in SEQ ID NO. 335; and    a polypeptide comprising an amino acid sequence being at least about 95% homologous to amino acids 1-110 of SEQ ID NO. 332.    
     
     
         6 . An isolated peptide, the peptide having a length “n”, wherein n is selected from the group consisting of 10 amino acids in length, 20 amino acids in length, 30 amino acids in length, 40 amino acids in length and 50 amino acids in length, wherein at least two amino acids comprise KR, having a structure as follows: a sequence starting from any of amino acid numbers 96-x to 96 of SEQ ID NO:363; and ending at any of amino acid numbers 97+((n-2)−x) of SEQ ID NO:363, in which x varies from 0 to n-2.  
     
     
         7 . An isolated peptide comprising the amino acid sequence set forth in a 50 amino acid long segment of SEQ ID NO:363 anywhere from amino acid position 48 to amino acid position 145, and including amino acids at positions 96 and 97.  
     
     
         8 . An isolated peptide comprising the amino acid sequence set forth in a 40 amino acid long segment of SEQ ID NO:363 anywhere from amino acid position 58 to amino acid position 135, and including amino acids at positions 96 and 97.  
     
     
         9 . An isolated peptide comprising the amino acid sequence set forth in a 30 amino acid long segment of SEQ ID NO:363 anywhere from amino acid position 68 to amino acid position 125, and including amino acids at positions 96 and 97.  
     
     
         10 . An isolated peptide comprising the amino acid sequence set forth in a 20 amino acid long segment of SEQ ID NO:363 anywhere from amino acid position 78 to amino acid position 115, and including amino acids at positions 96 and 97.  
     
     
         11 . An isolated peptide comprising the amino acid sequence set forth in a member selected from the group consisting of SEQ ID NOs 464, 465-471 and 472.  
     
     
         12 . An isolated primer pair, comprising the pair of nucleic acid sequences selected from the group consisting of: SEQ NOs 490 and 491; 41.6 and 417; 419 and 420.  
     
     
         13 . An antibody to specifically bind to the amino acid sequence of  claim 3 .  
     
     
         14 . An antibody to specifically bind to the amino acid sequence of  claim 4 .  
     
     
         15 . An antibody to specifically bind to the amino acid sequence of  claim 5 .  
     
     
         16 . A kit for detecting prostate cancer, comprising at least one primer pair of  claim 12 .  
     
     
         17 . A kit for detecting prostate cancer, comprising the antibody of  claim 13 .  
     
     
         18 . The kit of  claim 17 , wherein said kit further comprises at least one ELISA reagent or at least one Western blot reagent.  
     
     
         19 . A kit for detecting prostate cancer, comprising the antibody of  claim 14 .  
     
     
         20 . The kit of  claim 19 , wherein said kit further comprises at least one ELISA reagent or at least one Western blot reagent.  
     
     
         21 . A kit for detecting prostate cancer, comprising the antibody of  claim 15 .  
     
     
         22 . The kit of  claim 21 , wherein said kit further comprises at least one ELISA reagent or at least one Western blot reagent.  
     
     
         23 . A method for detecting prostate cancer, comprising detecting overexpression of the polynucleotide of  claim 1  in a sample from a patient.  
     
     
         24 . The method of  claim 23 , wherein said detecting overexpression comprises performing nucleic acid amplification.  
     
     
         25 . A method for detecting prostate cancer, comprising detecting overexpression of the polynucleotide of  claim 2  in a sample from a patient.  
     
     
         26 . The method of  claim 25 , wherein said detecting overexpression comprises performing nucleic acid amplification.  
     
     
         27 . A method for detecting prostate cancer, comprising detecting overexpression of the polypeptide of  claim 3  in a sample from a patient.  
     
     
         28 . The method of  claim 27 , wherein said detecting comprises detecting binding of the antibody of  claim 13  to the polypeptide of  claim 3  in a sample from a patient.  
     
     
         29 . A method for detecting prostate cancer, comprising detecting overexpression of the polypeptide of  claim 4  in a sample from a patient.  
     
     
         30 . The method of  claim 29 , wherein said detecting comprises detecting binding of the antibody of  claim 14  to the polypeptide of  claim 4  in a sample from a patient.  
     
     
         31 . A method for detecting prostate cancer, comprising detecting overexpression of the polypeptide of  claim 5  in a sample from a patient.  
     
     
         32 . The method of  claim 31 , wherein said detecting comprises detecting binding of the antibody of  claim 15  to the polypeptide of  claim 5  in a sample from a patient.  
     
     
         33 . A biomarker to detect prostate cancer, comprising an amino acid sequence of  claim 3 , marked with a label.  
     
     
         34 . A biomarker to detect prostate cancer, comprising an amino acid sequence of  claim 4 , marked with a label.  
     
     
         35 . A biomarker to detect prostate cancer, comprising an amino acid sequence of  claim 5 , marked with a label.  
     
     
         36 . A method to screen for prostate cancer, comprising detecting prostate cancer cells with the biomarker of  claim 33 .  
     
     
         37 . A method to screen for prostate cancer, comprising detecting prostate cancer cells with the biomarker of  claim 34 .  
     
     
         38 . A method to screen for prostate cancer, comprising detecting prostate cancer cells with the biomarker of  claim 35 .  
     
     
         39 . A method to diagnose prostate cancer, comprising detecting prostate cancer cells with the biomarker of  claim 33 .  
     
     
         40 . A method to diagnose prostate cancer, comprising detecting prostate cancer cells with the biomarker of  claim 34 .  
     
     
         41 . A method to diagnose prostate cancer, comprising detecting prostate cancer cells with the biomarker of  claim 35 .  
     
     
         42 . A method for monitoring disease progression, treatment efficacy or relapse of prostate cancer, comprising detecting prostate cancer cells with the biomarker of  claim 33 .  
     
     
         43 . A method for monitoring disease progression, treatment efficacy or relapse of prostate cancer, comprising detecting prostate cancer cells with the biomarker of  claim 34 .  
     
     
         44 . A method for monitoring disease progression, treatment efficacy or relapse of prostate cancer, comprising detecting prostate cancer cells with the biomarker of  claim 35 .  
     
     
         45 . A method of selecting a therapy for prostate cancer, comprising detecting prostate cancer cells with the biomarker of  claim 33  and selecting a therapy according to said detection.  
     
     
         46 . A method of selecting a therapy for prostate cancer, comprising detecting prostate cancer cells with the biomarker of  claim 34  and selecting a therapy according to said detection.  
     
     
         47 . A method of selecting a therapy for prostate cancer, comprising detecting prostate cancer cells with the biomarker of  claim 35  and selecting a therapy according to said detection.