NUCLEIC ACID-BASED METHODS AND COMPOSITIONS FOR THE DETECTION OF OVARIAN CANCER

• US 20090087849A1
• Filed: 09/05/2008
• Published: 04/02/2009
• Est. Priority Date: 09/06/2007
• Status: Abandoned Application

• Current Assignee: Tripath Imaging Incorporated (Becton Dickinson & Co)
• Original Assignee: Tripath Imaging Incorporated (Becton Dickinson & Co)
• Inventors: Fischer, Timothy J., Groelke, John W., Malinowski, Douglas P.
• Application Number:
  US12/205,464
• Publication Number:
  US 20090087849A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

Methods and compositions for identifying ovarian cancer in a patient sample are provided. The methods of the invention comprise detecting overexpression or underexpression of at least one nucleic acid biomarker in a body sample, wherein the biomarker is selectively overexpressed or underexpressed in ovarian cancer. The body sample may be, for example, an ovarian tissue sample. The biomarkers of the invention include any nucleic acid molecule that is selectively overexpressed in ovarian cancer, including, for example, MMP-7, PAEP, CA125, HE4, PLAUR, MUC-1, SLPI, SSP1, MSLN, SPON1, interleukin-7, folate receptor 1, claudin 3, inhibin A, inhibin BB, inhibin BA, and PAI-1. Overexpression or underexpression of a biomarker of interest is detected at the nucleic acid level using such methods as real-time PCR and various nucleic acid hybridization techniques. Kits for practicing the methods of the invention are further provided.

Claims

1. A method for diagnosing ovarian cancer in a patient, said method comprising detecting expression at the nucleic acid level of at least one biomarker in a body sample from the patient, wherein the overexpression of the biomarker distinguishes samples that are indicative of ovarian cancer from samples that are indicative of benign proliferation, and wherein said biomarker is selected from the group consisting of matrix metalloproteinase-7 (MMP-7), progesterone-associated endometrial protein (PALP), cancer antigen 125 (CA125), human epididymis 4 (HL4), plasminogen activator urokinase receptor (PLAUR), MUC-1, SLPI, osteopontin (SSP1), mesothelin (MSLN), SPON1, interleukin-7, folate receptor 1, and claudin 3.

2. The method of claim 1, further comprising detecting a plurality of biomarkers.

3. The method of claim 2, wherein the plurality of biomarkers is selected from the group consisting of:

(a) HL4 and CA125;

(b) PALP and CA125;

(c) HL4 and PALP; and

(d) HL4, PALP, and CA125.

4. The method of claim 1, wherein detecting expression of the biomarker comprises performing quantitative real-time PCR.

5. The method of claim 1, wherein detecting expression of the biomarker comprises performing nucleic acid hybridization.

6. The method of claim 1, wherein the sample is an ovarian tissue sample.

7. The method of claim 6, wherein the sample is from a frozen ovarian tissue sample or from a formalin-fixed, paraffin-embedded ovarian tissue sample.

8. The method of claim 1, wherein the at least one biomarker is selected from the group consisting of CA125, PAEP, MMP7, MUC-1, SLPI, SSP1, MSLN, folate receptor 1, and claudin 3.

9. The method of claim 8, wherein the method permits the identification of samples indicative of serous, endometrioid, mucinous, and clear cell ovarian carcinoma.

10. The method of claim 1, wherein the biomarker is PLAUR and the method permits the identification of samples indicative of serous, endometrioid, and mucinous ovarian carcinoma.

11. The method of claim 1, wherein the biomarker is interleukin-7 and the method permits the identification of samples indicative of mucinous ovarian carcinoma.

12. A method for diagnosing ovarian cancer in a patient, said method comprising detecting expression at the nucleic acid level of at least one biomarker in a body sample, wherein the underexpression of the biomarker distinguishes samples that are indicative of ovarian cancer from samples that are indicative of benign proliferation, and wherein said biomarker is inhibin A or PAI-1.

13. The method of claim 12, wherein the sample is an ovarian tissue sample.

14. The method of claim 12, wherein detecting expression of the biomarker comprises performing quantitative real-time PCR.

15. The method of claim 12, wherein detecting expression of the biomarker comprises performing nucleic acid hybridization.

16. The method of claim 12, wherein the biomarker is inhibin A and the method permits the identification of samples indicative of serous, endometrioid, mucinous, and clear cell ovarian carcinoma.

17. The method of claim 12, wherein the biomarker is PAI-1 and the method permits the identification of samples indicative of endometrioid and clear cell ovarian carcinoma.

18. A method for diagnosing ovarian cancer in a patient comprising detecting expression at the nucleic acid level of at least one biomarker in a body sample, wherein the overexpression of the biomarker distinguishes samples that are indicative of ovarian cancer from samples that are indicative of benign proliferation, and wherein said biomarker is selected from the group consisting of matrix metalloproteinase-7 (MMP-7), SLPI, SSP1, MSLN, SPON1, and MUC-1, and wherein the body sample from the patient displays low-levels of CA125 and PAEP mRNA.

19. The method of claim 18, wherein the sample is an ovarian tissue sample.

20. The method of claim 18, wherein detecting expression of the biomarker comprises performing quantitative real-time PCR.

21. The method of claim 18, wherein detecting expression of the biomarker comprises performing nucleic acid hybridization.