YKL-40 as a marker and prognostic indicator for cancers

• US 7,229,770 B1
• Filed: 10/01/1998
• Issued: 06/12/2007
• Est. Priority Date: 10/01/1998
• Status: Expired due to Fees

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Johansen, Julia S., Price, Paul A.
• Primary Examiner(s): UNGAR, SUSAN NMN
• Application Number:
  US09/164,862
• Time in Patent Office: 3,176 Days
• Field of Search: 435/7.23,7.1,387.1
• US Class Current: 435/7.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/57488 involving compounds identifable in body fluids

Abstract

This invention provides methods for detecting cancers and for evaluating the prognosis of cancer patients. In particular, the methods of this invention utilize YKL-40 as a marker for the presence or absence of a cancer and for the prognosis (e.g. likelihood of recurrence) of a cancer. Elevated levels of YKL-40 are indicative of the presence of a cancer in undiagnosed subjects and indicate likely recurrence of the cancer in subjects diagnosed as having a cancer.

Claims

1. A method for estimating survival expectancy of a cancer patient, said method comprising:

(a) obtaining a biological fluid sample comprising human YKL-40 from a cancer patient having at least a preliminary diagnosis of a cancer, wherein the sample is collected either prior to surgery for the cancer or at the time of first recurrence of the cancer, selected from the group consisting of a lung cancer, a bronchus cancer, a colorectal cancer, a prostate cancer, a pancreas cancer, a stomach cancer, an ovarian cancer, a urinary bladder cancer, a brain or an esophageal cancer, a cervical cancer, a melanoma, a uterine or endometrial cancer, a cancer of the oral cavity or pharynx, a liver cancer, a kidney cancer, a biliary tract cancer, a small bowel or appendix cancer, a salivary gland cancer, a thyroid gland cancer, an adrenal gland cancer, a testes cancer; and

(b) measuring the level of said YKL-40 in said sample and comparing the sample YKL-40 level to the YKL-40 level found in the same sample from normal healthy humans wherein a sample YKL-40 level above 95% of the YKL-40 levels in the same sample from said normal healthy humans is an indicator of a reduced survival expectancy compared to patients with normal YKL-40 level.

2. The method of claim 1, wherein said patient has a diagnosis of prostate cancer.

3. The method of claim 1, wherein said patient has a diagnosis of lung cancer.

4. The method of claim 1, wherein said patient has a diagnosis of a colorectal cancer.

5. The method of claim 4, wherein said patient is diagnosed with a Duke'"'"'s stage A colorectal cancer.

6. The method of claim 4, wherein said patient is diagnosed with a Duke'"'"'s stage B colorectal cancer.

7. The method of claim 4, wherein said patient is diagnosed with a Duke'"'"'s stage C colorectal cancer.

8. The method of claim 4, wherein said patient is diagnosed with a Duke'"'"'s stage D colorectal cancer.

9. The method of claim 1, wherein said biological sample is a sample selected from the group consisting of whole blood, plasma, serum, synovial fluid, cerebrospinal fluid, bronchial lavage, ascites fluid, bone marrow aspirate, pleural effusion, and urine.

10. The method of claim 1, wherein the level of YKL-40 is measured using an immunoassay.

11. The method of claim 10, wherein said immunoassay is a competitive immunoassay.

12. The method of claim 10, wherein said immunoassay is an ELISA.

13. The method of claim 10, wherein said immunoassay is a radioimmunoassay (RIA).

14. The method of claim 10, wherein said immunoassay uses a polyclonal anti-YKL-40 antibody.

15. The method of claim 10, wherein said immunoassay uses a monoclonal anti-YKL-40 antibody.

16. A method to screen for recurrence of a cancer after removal of a primary tumor, said method comprising:

(a) obtaining a biological fluid sample comprising human YKL-40 from a cancer patient following removal of a primary tumor selected from the group consisting of a lung cancer, a bronchus cancer, a prostate cancer, a pancreas cancer, a stomach cancer, an ovarian cancer, a urinary bladder cancer, a brain or central nervous system cancer, a peripheral nervous system cancer, an esophageal cancer, a cervical cancer, a melanoma, a uterine or endometrial cancer, a cancer of the oral cavity or pharynx, a liver cancer, a kidney cancer, a biliary tract cancer, a small bowel or appendix cancer, a salivary gland cancer, a thyroid gland cancer, an adrenal gland cancer, an osteosarcoma, a chondrosarcoma, a liposarcoma, a testes cancer, and a malignant fibrous histiocytoma; and

(b) measuring a level of YKL-40 in said sample and comparing the sample YKL-40 level to the YKL-40 level found in normal controls wherein a sample YKL-40 level above 95% of the YKL-40 levels in normal controls is an indicator of a possible recurrence of said cancer.

17. The method of claim 16, wherein said method is repeated at a multiplicity of instances after removal of said primary tumor.

26. The method of claim 16, wherein the level of YKL-40 is measured using an immunoassay.

18. A method of screening for an indicator for the presence of cancer, in a human, said method comprising:

(a) obtaining a biological sample comprising serum comprising YKL-40 from said human;

(b) measuring the level of YKL-40 in said serum and comparing the level to the YKL-40 level found in serum from normal healthy humans, wherein elevation in YKL-40 level in the sample being tested above 95% of the normal healthy humans, wherein said elevation is unrelated to known causes of YKL-40 elevation other than cancer, is an indicator of the presence of a cancer selected from the group consisting of a lung cancer, a bronchus cancer, a prostate cancer, a pancreas cancer, a stomach cancer, an ovarian cancer, a urinary bladder cancer, a brain or central nervous system cancer, a peripheral nervous system cancer, an esophageal cancer, a cervical cancer, a melanoma, a uterine or endometrial cancer, a cancer of the oral cavity or pharynx, a liver cancer, a kidney cancer, a biliary tract cancer, a small bowel or appendix cancer, a salivary gland cancer, a thyroid gland cancer, an adrenal gland cancer, an osteosarcoma, a chondrosarcoma, a liposarcoma, a testes cancer, or a malignant fibrous histiocytoma.

19. The method of claim 18, wherein said biological sample is a sample selected from the group consisting of whole blood, plasma, and serum.

20. The method of claim 18, wherein the level of YKL-40 is measured using an immunoassay.

21. The method of claim 20, wherein said immunoassay is a competitive immunoassay.

22. The method of claim 20, wherein said immunoassay is an ELISA.

23. The method of claim 20, wherein said immunoassay is a radioimmunoassay (RIA).

24. The method of claim 20, wherein said immunoassay uses a polyclonal anti-YKL-40 antibody.

25. The method of claim 20, wherein said immunoassay uses a monoclonal anti-YKL-40 antibody.