Identification of biomarkers for detecting pancreatic cancer

• US 20050095611A1
• Filed: 04/30/2004
• Published: 05/05/2005
• Est. Priority Date: 05/02/2003
• Status: Abandoned Application

• Current Assignee: Daniel W. Chan, Eric Fung, Jens Koopmann, Michael Goggins, White C. Nicole, Xiao-Ying Meng, Zhen Zhang
• Original Assignee: Daniel W. Chan, Eric Fung, Jens Koopmann, Michael Goggins, White C. Nicole, Xiao-Ying Meng, Zhen Zhang
• Inventors: Koopmann, Jens, White, C. Nicole, Zhang, Zhen, Meng, Xiao-Ying, Fung, Eric, Chan, Daniel W., Goggins, Michael
• Application Number:
  US10/836,649
• Publication Number:
  US 20050095611A1
• Time in Patent Office: Days
• US Class Current: 435/6.12
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 33/57438 of liver, pancreas or kidney

Abstract

The present invention relates to a method of qualifying pancreatic cancer status in a subject comprising: (a) measuring at least one of the disclosed biomarkers in a sample from the subject and (b) correlating the measurement with pancreatic cancer status. The invention further relates to kits for qualifying pancreatic cancer status in a subject.

Claims

1. A method of qualifying pancreatic cancer status in a subject comprising:

(a) measuring at least one biomarker in a sample from the subject, wherein the biomarker is selected from the group consisting of

Marker I;

having a molecular weight of about 3.667 kD

Marker II;

having a molecular weight of about 7.441 kD

Marker III;

having a molecular weight of about 3.146 kD

Marker IV;

having a molecular weight of about 12.861 kD

Marker V;

having a molecular weight of about 3.760 kD

Marker VI;

having a molecular weight of about 4.053 kD

Marker VII;

having a molecular weight of about 5.884 kD

Marker VIII;

having a molecular weight of about 6.081 kD

Marker IX;

having a molecular weight of about 3.473 kD

Marker X;

having a molecular weight of about 5.903 kD

Marker XI;

having a molecular weight of about 8.563 kD

Marker XII;

having a molecular weight of about 16.008 kD

Marker XIII;

having a molecular weight of about 4.159 kD

Marker XIV;

having a molecular weight of about 4.179 kD

Marker XV;

having a molecular weight of about 7.607 kD

Marker XVI;

having a molecular weight of about 4.277 kD

Marker XVII;

having a molecular weight of about 4.639 kD

Marker XVIII;

having a molecular weight of about 6.093 kD

Marker XIX;

having a molecular weight of about 7.463 kD

Marker XX;

having a molecular weight of about 9.132 kD

Marker XXI;

having a molecular weight of about 3.885 kD

Marker XXII;

having a molecular weight of about 3.967 kD

Marker XXIII;

having a molecular weight of about 8.929 kD

Marker XXIV;

having a molecular weight of about 3.370 kD

Marker XXV;

having a molecular weight of about 3.441 kD

Marker XXVI;

having a molecular weight of about 10.055 kD

Marker XXVII;

having a molecular weight of about 3.510 kD

Marker XXVIII;

having a molecular weight of about 9.120 kD

Marker XXIX;

having a molecular weight of about 7.294 kD

Marker XXX;

having a molecular weight of about 8.866 kD

Marker XXXI;

having a molecular weight of about 9.401 kD

Marker XXXII;

having a molecular weight of about 8.754 kD, and combinations thereof, and

(b) correlating the measurement with pancreatic cancer status.

2. The method of claim 1 further comprising:

(c) managing subject treatment based on the status.

3. The method of claim 2, wherein managing subject treatment is selected from ordering more tests, performing surgery, and taking no further action.

4. The method of claim 2 further comprising:

(d) measuring the at least one biomarker after subject management.

5. The method of claim 1 wherein the pancreatic cancer status is selected from the group consisting of the subject'"'"'s risk of cancer, the presence or absence of disease, the type of disease, the stage of disease and the effectiveness of treatment of disease.

22. The method of claim 1 further comprising measuring a known biomarker.

23. The method of claim 22, wherein the known biomarker is CA19-9.

24. The method of any of claim 1 wherein the marker is detected by mass spectrometry.

25. The method of any of claim 1 wherein the marker is detected by capturing the marker on a biochip having an affinity surface and detecting the captured marker by SELDI.

29. The method of claim 1 wherein the patient sample is selected from the group consisting of blood, blood plasma, serum, urine, tissue, cells, organs and seminal fluids.

31. The method of claim 1 comprising:

generating data on immobilized subject samples on a biochip, by subjecting said biochip to laser ionization and detecting intensity of signal for mass/charge ratio; and

,

transforming the data into computer readable form;

executing an algorithm that classifies the data according to user input parameters, for detecting signals that represent biomarkers present in pancreatic cancer patients and are lacking in non-cancer subject controls.

32. The method of claim 1 wherein one or more of the biomarkers are detected using laser desorption/ionization mass spectrometry, comprising:

providing a probe adapted for use with a mass spectrometer comprising an adsorbent attached thereto;

contacting the subject sample with the adsorbent;

desorbing and ionizing the biomarker or biomarkers from the probe; and

,

detecting the deionized/ionized markers with the mass spectrometer.

33. :

The method of claim 32, wherein the adsorbent is hydrophobic, hydrophilic, ionic or metal chelate adsorbent.

34. The method of claim 33, wherein the adsorbent is comprised of copper.

35. The method of claim 32, wherein the adsorbent is an antibody, single- or double stranded oligonucleotide, amino acid, protein, peptide or fragments thereof.

36. The method of claim 1, wherein at least one or more protein biomarkers are detected using immunoassays.

6-21. -21. (canceled).

26-28. -28. (canceled).

30. (canceled).

37. A process for purification of a biomarker, comprising fractioning a sample comprising one or more protein biomarkers by size-exclusion chromatography and collecting a fraction that includes the one or more biomarker;

and/or fractionating a sample comprising the one or more biomarkers by anion exchange chromatography and collecting a fraction that includes the one or more biomarkers, wherein the biomarker is selected from;

Marker I;

having a molecular weight of about 3.667 kD

Marker II;

having a molecular weight of about 7.441 kD

Marker III;

having a molecular weight of about 3.146 kD

Marker IV;

having a molecular weight of about 12.861 kD

Marker V;

having a molecular weight of about 3.760 kD

Marker VI;

having a molecular weight of about 4.053 kD

Marker VII;

having a molecular weight of about 5.884 kD

Marker VIII;

having a molecular weight of about 6.081 kD

Marker IX;

having a molecular weight of about 3.473 kD

Marker X;

having a molecular weight of about 5.903 kD

Marker XI;

having a molecular weight of about 8.563 kD

Marker XII;

having a molecular weight of about 16.008 kD

Marker XIII;

having a molecular weight of about 4.159 kD

Marker XIV;

having a molecular weight of about 4.179 kD

Marker XV;

having a molecular weight of about 7.607 kD

Marker XVI;

having a molecular weight of about 4.277 kD

Marker XVII;

having a molecular weight of about 4.639 kD

Marker XVIII;

having a molecular weight of about 6.093 kD

Marker XIX;

having a molecular weight of about 7.463 kD

Marker XX;

having a molecular weight of about 9.132 kD

Marker XXI;

having a molecular weight of about 3.885 kD

Marker XXII;

having a molecular weight of about 3.967 kD

Marker XXIII;

having a molecular weight of about 8.929 kD

Marker XXIV;

having a molecular weight of about 3.370 kD

Marker XXV;

having a molecular weight of about 3.441 kD

Marker XXVI;

having a molecular weight of about 10.055 kD

Marker XXVII;

having a molecular weight of about 3.510 kD

Marker XXVIII;

having a molecular weight of about 9.120 kD

Marker XXIX;

having a molecular weight of about 7.294 kD

Marker XXX;

having a molecular weight of about 8.866 kD

Marker XXXI;

having a molecular weight of about 9.401 kD

Marker XXXII;

having a molecular weight of about 8.754 kD, and combinations thereof.

38-54. -54. (canceled).

55. A protein purified on a biochip selected from:

Marker I;

having a molecular weight of about 3.667 kD

Marker II;

having a molecular weight of about 7.441 kD

Marker III;

having a molecular weight of about 3.146 kD

Marker IV;

having a molecular weight of about 12.861 kD

Marker V;

having a molecular weight of about 3.760 kD

Marker VI;

having a molecular weight of about 4.053 kD

Marker VII;

having a molecular weight of about 5.884 kD

Marker VIII;

having a molecular weight of about 6.081 kD

Marker IX;

having a molecular weight of about 3.473 kD

Marker X;

having a molecular weight of about 5.903 kD

Marker XI;

having a molecular weight of about 8.563 kD

Marker XII;

having a molecular weight of about 16.008 kD

Marker XIII;

having a molecular weight of about 4.159 kD

Marker XIV;

having a molecular weight of about 4.179 kD

Marker XV;

having a molecular weight of about 7.607 kD

Marker XVI;

having a molecular weight of about 4.277 kD

Marker XVII;

having a molecular weight of about 4.639 kD

Marker XVIII;

having a molecular weight of about 6.093 kD

Marker XIX;

having a molecular weight of about 7.463 kD

Marker XX;

having a molecular weight of about 9.132 kD

Marker XXI;

having a molecular weight of about 3.885 kD

Marker XXII;

having a molecular weight of about 3.967 kD

Marker XXIII;

having a molecular weight of about 8.929 kD

Marker XXIV;

having a molecular weight of about 3.370 kD

Marker XXV;

having a molecular weight of about 3.441 kD

Marker XXVI;

having a molecular weight of about 10.055 kD

Marker XXVII;

having a molecular weight of about 3.510 kD

Marker XXVIII;

having a molecular weight of about 9.120 kD

Marker XXIX;

having a molecular weight of about 7.294 kD

Marker XXX;

having a molecular weight of about 8.866 kD

Marker XXXI;

having a molecular weight of about 9.401 kD, and

Marker XXXII;

having a molecular weight of about 8.754 kD.

56-73. -73. (canceled).

74. A method comprising:

(a) measuring a plurality of biomarkers in a sample from the subject, wherein the biomarkers are selected from the group consisting of;

Marker I;

having a molecular weight of about 3.667 kD

Marker II;

having a molecular weight of about 7.441 kD

Marker III;

having a molecular weight of about 3.146 kD

Marker IV;

having a molecular weight of about 12.861 kD

Marker V;

having a molecular weight of about 3.760 kD

Marker VI;

having a molecular weight of about 4.053 kD

Marker VII;

having a molecular weight of about 5.884 kD

Marker VIII;

having a molecular weight of about 6.081 kD

Marker IX;

having a molecular weight of about 3.473 kD

Marker X;

having a molecular weight of about 5.903 kD

Marker XI;

having a molecular weight of about 8.563 kD

Marker XII;

having a molecular weight of about 16.008 kD

Marker XIII;

having a molecular weight of about 4.159 kD

Marker XIV;

having a molecular weight of about 4.179 kD

Marker XV;

having a molecular weight of about 7.607 kD

Marker XVI;

having a molecular weight of about 4.277 kD

Marker XVII;

having a molecular weight of about 4.639 kD

Marker XVIII;

having a molecular weight of about 6.093 kD

Marker XIX;

having a molecular weight of about 7.463 kD

Marker XX;

having a molecular weight of about 9.132 kD

Marker XXI;

having a molecular weight of about 3.885 kD

Marker XXII;

having a molecular weight of about 3.967 kD

Marker XXIII;

having a molecular weight of about 8.929 kD

Marker XXIV;

having a molecular weight of about 3.370 kD

Marker XXV;

having a molecular weight of about 3.441 kD

Marker XXVI;

having a molecular weight of about 10.055 kD

Marker XXVII;

having a molecular weight of about 3.510 kD

Marker XXVIII;

having a molecular weight of about 9.120 kD

Marker XXIX;

having a molecular weight of about 7.294 kD

Marker XXX;

having a molecular weight of about 8.866 kD

Marker XXXI;

having a molecular weight of about 9.401 kD, and

Marker XXXII;

having a molecular weight of about 8.754 kD, and combinations thereof.

75-104. -104. (canceled).

105. A method for identifying a compound capable of treating pancreatic cancer comprising:

a) contacting at least one biomarker selected from the group consisting of

Marker I;

having a molecular weight of about 3.667 kD

Marker II;

having a molecular weight of about 7.441 kD

Marker III;

having a molecular weight of about 3.146 kD

Marker IV;

having a molecular weight of about 12.861 kD

Marker V;

having a molecular weight of about 3.760 kD

Marker VI;

having a molecular weight of about 4.053 kD

Marker VII;

having a molecular weight of about 5.884 kD

Marker VIII;

having a molecular weight of about 6.081 kD

Marker IX;

having a molecular weight of about 3.473 kD

Marker X;

having a molecular weight of about 5.903 kD

Marker XI;

having a molecular weight of about 8.563 kD

Marker XII;

having a molecular weight of about 16.008 kD

Marker XIII;

having a molecular weight of about 4.159 kD

Marker XIV;

having a molecular weight of about 4.179 kD

Marker XV;

having a molecular weight of about 7.607 kD

Marker XVI;

having a molecular weight of about 4.277 kD

Marker XVII;

having a molecular weight of about 4.639 kD

Marker XVIII;

having a molecular weight of about 6.093 kD

Marker XIX;

having a molecular weight of about 7.463 kD

Marker XX;

having a molecular weight of about 9.132 kD

Marker XXI;

having a molecular weight of about 3.885 kD

Marker XXII;

having a molecular weight of about 3.967 kD

Marker XXIII;

having a molecular weight of about 8.929 kD

Marker XXIV;

having a molecular weight of about 3.370 kD

Marker XXV;

having a molecular weight of about 3.441 kD

Marker XXVI;

having a molecular weight of about 10.055 kD

Marker XXVII;

having a molecular weight of about 3.510 kD

Marker XXVIII;

having a molecular weight of about 9.120 kD

Marker XXIX;

having a molecular weight of about 7.294 kD

Marker XXX;

having a molecular weight of about 8.866 kD

Marker XXXI;

having a molecular weight of about 9.401 kD

Marker XXXII;

having a molecular weight of about 8.754 kD, and combinations thereof

with a test compound; and

b) determining whether the test compound binds to the biomarker, wherein a compound that binds to the biomarker is identifies as a compound capable of treated pancreatic cancer.

106-112. -112. (canceled).