METHODS OF SCREENING FOR GASTROINTESTINAL CANCER

• US 20080057514A1
• Filed: 09/05/2007
• Published: 03/06/2008
• Est. Priority Date: 09/06/2006
• Status: Active Grant

• Current Assignee: Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Goldenring, James
• Granted Patent: US 7,811,778 B2
• 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 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism

Abstract

Methods for diagnosing an upper gastrointestinal (GI) cancer in a subject by determining an amount of one or more biomarkers in a biological sample from the subject are provided. Methods for determining whether to initiate or continue prophylaxis or treatment of an upper GI cancer in a subject by determining any measurable change in the amounts of the at least one biomarker in each of a series of biological samples provided over a time period are also provided.

Claims

1. A method for diagnosing an upper gastrointestinal (GI) cancer in a subject, comprising:

(a) providing a biological sample from the subject;

(b) determining an amount in the sample of at least one biomarker selected from the group consisting of HE4, LGALS3, IL1RN, TRIP13, FIGNL1, CRIP1, S100A4, EXOSC8, EXPI, BRRN1, NELF, EREG, TMEM40, and TMEM109; and

(c) comparing the amount in the sample of the at least one biomarker, if present to a control level of the at least one biomarker, wherein the subject is diagnosed as having an upper GI cancer if there is a measurable difference in the amount of the at least one biomarker in the sample as compared to the control level.

2. The method of claim 1, wherein the upper GI cancer is a cancer selected from the group consisting of gastric cancer, pancreatic cancer, and esophageal cancer.

3. The method of claim 1, wherein the biological sample comprises blood, serum, plasma, gastric secretions, an upper GI biopsy sample, microdissected cells from an upper GI biopsy, upper GI cells sloughed into the GI lumen, and upper GI cells recovered from stool.

4. The method of claim 1, wherein the at least one biomarker is HE4.

5. The method of claim 1, comprising further determining an amount in the sample of a TFF2 biomarker.

6. The method of claim 1, wherein determining the amount of the at least one biomarker comprises one or more techniques selected from:

(a) determining an amount of mRNA of the at least one biomarker in the biological sample using an RNA measuring assay; and

(b) determining an amount of a polypeptide of the at least one biomarker in the biological sample using a protein measuring assay.

7. The method of claim 6, wherein the RNA measuring assay comprises an array of RNA hybridization probes or a quantitative polymerase chain reaction assay.

8. The method of claim 6, wherein the protein measuring assay comprises mass spectrometry (MS) analysis, immunoassay analysis, or both.

9. The method of claim 8, wherein the immunoassay analysis comprises one or more antibodies that selectively bind at least one biomarker.

10. The method of claim 1, further comprising selecting a treatment or modifying a treatment for the upper GI cancer based on the amount of the at least one biomarker determined.

11. A method for determining whether to initiate or continue prophylaxis or treatment of an upper gastrointestinal (GI) cancer in a subject comprising:

(a) providing a series of biological samples over a time period from the subject;

(b) analyzing the series of biological samples to determine an amount of at least one biomarker selected from the group consisting of HE4, LGALS3, IL1RN, TRIP13, FIGNL1, CRIP1, S100A4, EXOSC8, EXPI, BRRN1, NELF, EREG, TMEM40, and TMEM109 in each of the biological samples; and

(c) determining any measurable change in the amount of the at least one biomarker in each of the biological samples to thereby determine whether to initiate or continue the prophylaxis or therapy of the upper GI cancer.

12. The method of claim 11, wherein the upper GI cancer is a cancer selected from the group consisting of gastric cancer, pancreatic cancer, and esophageal cancer.

13. The method of claim 11, wherein the biological sample comprises blood, serum, plasma, gastric secretions, an upper GI biopsy sample, microdissected cells from an upper GI biopsy, upper GI cells sloughed into the GI lumen, and upper GI cells recovered from stool.

14. The method of claim 11, wherein the at least one biomarker is HE4.

15. The method of claim 11, comprising further analyzing the series of biological samples to determine an amount of a TFF2 biomarker in each of the biological samples.

16. The method of claim 11, wherein the series of biological samples comprises a first biological sample collected prior to initiation of the prophylaxis or treatment for the upper GI cancer and a second biological sample collected after initiation of the prophylaxis or treatment.

17. The method of claim 11 wherein analyzing the series of biological samples to determine the amount of the at least one biomarker in each of the samples comprises one or more techniques selected from:

(a) determining an amount of mRNA of the at least one biomarker in each of the biological samples using an RNA measuring assay; and

(b) determining an amount of a polypeptide of the at least one biomarker in each of the biological samples using a protein measuring assay.

18. The method of claim 17, wherein the RNA measuring assay comprises an array of RNA hybridization probes or a quantitative polymerase chain reaction assay.

19. The method of claim 17, wherein the protein measuring assay comprises mass spectrometry (MS) analysis, immunoassay analysis, or both.

20. The method of claim 19, wherein the immunoassay analysis comprises one or more antibodies that selectively bind the at least one biomarker.

21. A kit for diagnosing an upper gastrointestinal (GI) cancer in a subject, the kit comprising probes for selectively binding each of one or more biomarkers selected from HE4, LGALS3, IL1RN, TRIP13, FIGNL1, CRIP1, S100A4, EXOSC8, EXPI, BRRN1, NELF, EREG, TMEM40, and TMEM109.

22. The kit of claim 21, wherein the probes are bound to a substrate.

23. The kit of claim 21, wherein the probes are labeled to allow for detecting the binding of the probes to the one or more biomarkers.

24. The kit of claim 21, wherein the probes are RNA hybridization probes.

25. The kit of claim 21, wherein the probes are antibodies.