Use of biomarkers for detecting ovarian cancer

1. A method of determining if a subject has ovarian cancer comprising:

(a) measuring in a sample from the subject the amount of apolipoprotein A1 (ApoA1) and of a cleavage fragment of inter-α-trypsin inhibitor heavy chain H4 (IAIH4 fragment), wherein the IAIH4 fragment consists of the amino acid sequence of SEQ ID NO: 1 and

(b) comparing the amounts measured in step (a) with the amount of ApoA1 and of IAIH4 fragment measured in a sample from a control, wherein a decrease in the amount of ApoA1 in the sample as compared to the control sample, and an increase in the amount of IAIH4 fragment in the sample as compared to the control sample indicates that the subject has ovarian cancer.

2. The method of claim 1 further comprising: (c) managing subject treatment based on the presence of ovarian canter.

3. The method of claim 2 , wherein managing subject treatment is selected from the group consisting of: ordering more tests, and taking no further action.

4. The method of claim 2 further comprising:

(d) measuring the amount of ApoA1 or IAIH4 fragment after subject management.

5. The method of claim 1 further comprising measuring at least one additional biomarker in the sample from the subject.

6. The method of claim 5 , wherein the additional biomarker is selected from the group consisting of: CA125, CA125 II, CA15-3, CA19-9, CA72-4, CA 195, tumor associated trypsin inhibitor (TATI), CEA, placental alkaline phosphatase (PLAP), Sialyl TN, galactosyltransferase, macrophage colony stimulating factor (M-CSF, CSF-1), lysophosphatidic acid (LPA), 110 kD component of the extracellular domain of the epidermal growth factor receptor (pi 10EGFR), tissue kallikreins, e.g., kallikrein 6 and kallikrein 10 (NES-1), prostasin, HE4, creatine kinase B (CKB), LASA, HER-2/neu, urinary gonadotropin peptide, Dianon NB 70/K, Tissue peptide antigen (TPA), osteopontin and haptoglobin.

7. The method of claim 5 wherein the additional biomarker is CA125.

8. The method of claim 1 wherein measuring comprises:

(a) providing a subject sample of blood or a blood derivative;

(b) fractionating proteins in the sample on an anion exchange resin and collecting fractions that contain ApoA1 and IAIH4 fragment;

(c) capturing ApoA1 and IAIH4 fragment from the fractions on a surface of a substrate comprising capture reagents that bind the protein biomarkers; and

(d) determining the amount of ApoA1 and IAIH4 fragment that is present on the surface of the substrate, thereby determining the amount of ApoA1 and IAIH4 fragment that is present in the sample.

9. The method of claim 8 wherein the substrate is a SELDI probe comprising an IMAC copper surface and wherein the protein biomarkers are detected by SELDI.

10. The method of claim 8 wherein the substrate is a SELDI probe comprising biospecific affinity reagents that bind ApoA1 and IAIH4 fragment and wherein ApoA1 and IAIH4 fragment are detected by SELDI.

11. The method of claim 8 wherein the substrate is a microtiter plate comprising biospecific affinity reagents that bind ApoA1 and IAIH4 fragment and ApoA1 and IAIH4fragment are detected by immunoassay.

12. The method of claim 1 wherein at least one of ApoA1 and IAIH4 fragment is measured using a biochip array.

13. The method of claim 12 wherein the biochip array is a protein chip array.

14. The method of claim 12 wherein ApoA1 or IAIH4 fragment is immobilized on the biochip array.

15. The method of claim 1 wherein ApoA1 and IAIH4 fragment are measured by SELDI.

16. The method of claim 1 wherein ApoA1 and IAIH4 fragment are measured by immunoassay.

17. The method of claim 1 wherein classification of a patient as having ovarian cancer is performed by a software classification algorithm.

18. The method of claim 1 wherein the sample is selected from blood, serum and plasma.

19. A method of qualifying ovarian cancer status in a subject comprising:

(a) measuring in a sample from the subject the amount of ApoA1 and of IAIH4 fragment, wherein the IAIH4 fragment consists of the amino acid sequence of SEQ ID NO: 1, and

(b) comparing the amounts measured in step (a) with the amount of ApoA1 and of IAIH4 fragment measured in a sample from a control, wherein ovarian cancer status is the presence or absence of ovarian cancer, wherein a decrease in the amount of ApoA1 in the sample as compared to the control sample, and an increase in the amount of IAIH4 fragment in the sample as compared to the control sample is indicative of the presence of ovarian cancer in the subject.

20. The method of claim 19 further comprising: (c) managing subject treatment based on the presence or absence of ovarian cancer in the subject.

21. The method of claim 20 wherein managing subject treatment is selected from ordering more tests, and taking no further action.

22. The method of claim 20 further comprising:

(d) measuring ApoA1 or IAIH4 fragment after subject management.

23. The method of claim 19 wherein the amount of ApoA1 and of the IAIH4 fragment is measured in a sample from a subject who has been previously treated for ovarian cancer.

24. The method of claim 19 further comprising measuring at least one additional biomarker in the sample from the subject.

25. The method of claim 24 wherein the additional biomarker is selected from CA125, CA125 II, CA15-3, CA19-9, CA72-4, CA 195, tumor associated trypsin inhibitor (TATI), CEA, placental alkaline phosphatase (PLAP), Sialyl TN, galactosyltransferase, macrophage colony stimulating factor (M-CSF, CSF-1), lysophosphatidic acid (LPA), 110 kD component of the extracellular domain of the epidermal growth factor receptor (p110EGFR), tissue kallikreins, e.g., kallikrein 6 and kallikrein 10 (NES-1), prostasin, HE4, creatine kinase B (CKB), LASA, HER-2/neu, urinary gonadotropin peptide, Dianon NB 70/K, Tissue peptide antigen (TPA), osteopontin and haptoglobin.

26. The method of claim 24 wherein the additional biomarker is CA125.

27. The method of claim 19 wherein measuring comprising:

(a) providing a subject sample of blood or a blood derivative;

(b) fractionating proteins in the sample on an anion exchange resin and collecting fractions that contain ApoA1 and IAIH4 fragment;

(c) capturing ApoA1 and IAIH4 fragment from the fractions on a surface of a substrate comprising capture reagents that bind the protein; and

(d) determining the amount of ApoA1 and IAIH4 fragment that is present on the surface of the substrate, thereby determining the amount of ApoA1 and IAIH4 fragment that is present in the sample.

28. The method of claim 27 wherein the substrate is a SELDI probe comprising an IMAC copper surface and wherein ApoA1 and IAIH4 fragment are detected by SELDI.

29. The method of claim 27 wherein the substrate is a SELDI probe comprising biospecific affinity reagents that bind ApoA1 and IAIH4 fragment and wherein ApoA1 and IAIH4 fragment are detected by SELDI.

30. The method of claim 27 wherein the substrate is a microtiter plate comprising biospecific affinity reagents that bind ApoA1 and IAIH4 fragment and ApoA1 and IAIH4 fragment are detected by immunoassay.

31. The method of claim 19 wherein ApoA1 or IAIH4 fragment is measured using a biochip array.

32. The method of claim 31 wherein the biochip array is a protein chip array.

33. The method of claim 31 wherein or IAIH4 fragment is immobilized on the biochip array.

34. The method of claim 19 wherein ApoA1 or IAIH4 fragment are measured by SELDI.

35. The method of claim 19 wherein ApoA1 or IAIH4 fragment are measured by immunoassay.