Method for biomarker and drug-target discovery for prostate cancer diagnosis and treatment as well as biomarker assays determined therewith

Patent metadata

Field	Value
Publication number	US-2016274117-A1
Application number	US-201615170876-A
Country	US
Kind code	A1
Filing date	Jun 1, 2016
Priority date	May 14, 2008
Publication date	Sep 22, 2016
Grant date	—

Abstract

The invention relates to biomarker assays based on protein/peptide biomarkers which show a pronounced differential behaviour between healthy and cancerous sample proteomes e.g. by mass spectrometric measurement and/or antibody-based assays such as an Enzyme-Linked Immunosorbent Assay (ELISA) determination of the protein biomarkers in serum, plasma or blood itself.

First claim

1 .- 6 . (canceled)

7 . A cancer biomarker assay comprising a combined measurement of at least two protein biomarkers selected from the group consisting of THBS1, HYOU1, ICAM1, CTSD, OLFM4 and TIMP1 in human serum, plasma or blood.

8 . A method for risk assessment, therapy and/or monitoring of treatment of cancer of a subject comprising:
a first step of measuring concentrations of at least two proteins selected from the group consisting of THBS1, HYOU1, CTSD, OLFM4, ICAM1, and TIMP1 in human serum, plasma or blood, the first step being performed by contacting the human serum, plasma, or blood with an affinity reagent for each protein and detecting whether binding occurs between the proteins and the affinity reagent using a quantitative readout; a second step of correlating the concentrations of the proteins measured in the first step with a predetermined cancer threshold concentration value for each of the proteins; and a third step of assessing the risk of cancer of the subject, treating the subject and/or monitoring of treatment of the subject.

9 . The method according to claim 8 ,
wherein the predetermined cancer threshold concentration value of the THBS1 is more than 12500 ng/ml, and/or the predetermined cancer threshold concentration value of the CTSD is less than 32 ng/ml, and/or the predetermined cancer threshold concentration value of the OLFM4 is less than 20 ng/ml, and/or the predetermined cancer threshold concentration value of the ICAM1 is less than 360 ng/ml, and/or the predetermined cancer threshold concentration value of the HYOU1 is more than 35 ng/ml.

10 . A method for risk assessment, therapy and/or monitoring of treatment of localized prostate cancer for distinction from benign prostate hyperplasia, the method comprising:
a first step of measuring (i) concentrations of at least three proteins or fragments thereof, the at least three proteins being selected from the group consisting of THBS1, HYOU1, ICAM1, CTSD, OLFM4 and TIMP1 in human serum, plasma or blood, or (ii) a concentration of a Prostate Specific Antigen (PSA) in the human serum, plasma or blood using an affinity reagent-based assay, a second step of correlating the concentrations of the proteins or the fragments thereof with a predetermined cancer threshold concentration value for each of the proteins or correlating the concentration of the Prostate Specific Antigen with a predetermined cancer threshold concentration value of the Prostate Specific Antigen; and a third step of assessing the risk of localized prostate cancer of the subject, treating the subject and/or monitoring of treatment of the subject.

11 . The method according to claim 10 , wherein
the predetermined cancer threshold concentration of the CTSD is less than 25 ng/ml, and/or the predetermined cancer threshold concentration value of the THBS1 is more than 13500 ng/ml, and/or said predetermined cancer threshold concentration value of the OLFM4 is less than 15 ng/ml, and/or said predetermined cancer threshold concentration value of the ICAM1 is less than 340 ng/ml, and/or said predetermined cancer threshold concentration value of the HYOU1 is more than 35 ng/ml.

12 . The method according to claim 8 further comprising:
measuring a concentration of at least one protein selected from the group consisting of ASPN, VTN, AOC3, LOX, PGCP, PSAP, CFH, CLU, KIT, TFRC, LGALS3BP, GOLPH2, AKAP13, CP, CPE, CPM, MSMB, TM9SF3, GALNTL4, GSPT1, CEACAM1 and EFNA5.

13 . The method according to claim 8 , wherein in the first step the concentrations of at least three proteins selected from the group consisting of THBS1, HYOU1, ICAM1, CTSD, OLFM4 and TIMP1 are measured.

14 . The method according to claim 8 , wherein
the predetermined cancer threshold concentration value of the CTSD is more than 120 ng/ml, and the predetermined cancer threshold concentration value of the THBS1 is less than 12000 ng/ml.

15 . The method according to claim 10 , wherein the concentration of the Prostate Specific Antigen (PSA) is measured using an antibody-based Enzyme-Linked Immunosorbent Assay (ELISA), and the predetermined cancer threshold concentration value of the Prostate Specific Antigen is more than 2 ng/ml.

16 . The method according to claim 8 , wherein in the first step, the concentrations of THBS1, ICAM1, CTSD and OLFM4 are measured.

17 . The cancer biomarker assay according to claim 7 , further comprising an affinity reagent-based antibody-based assay for detecting of Prostate Specific Antigen (PSA).

18 . The method according to claim 8 , wherein in the first step, the concentrations of at least three proteins selected from the group consisting of THBS1, CTSD, OLFM4 and ICAM1 are measured.

19 . The method according to claim 8 , wherein the first step is carried out using an Enzyme-Linked Immunosorbent Assay (ELISA).

20 . The method according to claim 8 , wherein the first step is performed by measuring the concentrations of at least three proteins selected from the group consisting of THBS1, CTSD, OLFM4 and ICAM1, and a concentration of one further protein selected from the group consisting of AOC3, LOX, PGCP, PSAP, CFH, CLU, KIT, TFRC, LGALS3BP, GOLPH2 and HYOU1.

21 . The method according to claim 15 , wherein for a positive diagnosis the predetermined cancer threshold concentration value of the Prostate Specific Antigen has to be more than 4 ng/ml.

22 . The method according to claim 15 , wherein for a positive diagnosis the predetermined cancer threshold concentration value of the Prostate Specific Antigen has to be more than 100 ng/ml.

23 . The method according to claim 15 , wherein for a positive diagnosis the predetermined cancer threshold concentration value of the Prostate Specific Antigen has to be more than 175 ng/ml.

24 . The method according to claim 8 , wherein the method is for distinguishing localized prostate cancer from benign prostate hyperplasia.

25 . The method according to claim 8 , wherein in the first step, the concentrations of at least three proteins selected from the group consisting of THBS1, HYOU1, CTSD and OLFM4 are measured.

26 . A method for personalized medicine, applied to a subject comprising:
a first step of measuring concentrations of at least two proteins selected from the group consisting of THBS1, HYOU1, CTSD, OLFM4, ICAM1 and TIMP1 in human serum, plasma or blood of said subject, the first step being performed by contacting the human serum, plasma, or blood with an affinity reagent for each protein and detecting whether binding occurs between the proteins and the affinity reagent using a quantitative readout; a second step of correlating the concentrations of the proteins measured in the first step with a predetermined cancer threshold concentration value for each of the proteins; and a third step of assessing the risk of cancer of the subject, treating the subject and/or monitoring of treatment of the subject.

27 . A method for detecting a predetermined concentration of at least two proteins selected from the group consisting of THBS1, HYOU1, ICAM1, CTSD, OLFM4 and TIMP1 in a subject, the method comprising:
obtaining a serum, plasma or blood sample from the subject; and detecting whether the predetermined concentration of the at least two proteins is present in the serum, plasma or blood sample by contacting the serum, plasma or blood sample with an affinity reagent for each protein and detecting binding between the at least two proteins and the affinity reagent, wher

Assignees

• Eth Zuerich
• St Gallen Kantonsspital

Inventors

• Krek Wilhelm
• Cima Igor
• Aebersold Rudolf
• Schiess Ralph
• Cerny Thomas
• Gillessen Silke

Classifications

• G01N33/57557 Primary

  of other specific parts of the body, e.g. brain · CPC title

• G01N33/57555 Primary

  of the prostate · CPC title

• G01N2333/70525

  ICAM molecules, e.g. CD50, CD54, CD102 · CPC title

• G01N2333/47

  Assays involving proteins of known structure or function as defined in the subgroups · CPC title

• G01N2333/8146

  Metalloprotease (E.C. 3.4.24) inhibitors, e.g. tissue inhibitor of metallo proteinase, TIMP · CPC title