Markers for detection of gastric cancer

• US 20070184439A1
• Filed: 07/16/2004
• Published: 08/09/2007
• Est. Priority Date: 07/17/2003
• Status: Active Grant

• Current Assignee: Pacific Edge Ltd.
• Original Assignee: Pacific Edge Ltd.
• Inventors: Holyoake, Andrew, Guilford, Parry
• Granted Patent: US 10,179,935 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• 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
• CPC Class Codes: C12Q 2600/16 Primer sets for multiplex assays
• CPC Class Codes: G01N 33/57446 of stomach or intestine

Abstract

Early detection of tumors is a major determinant of survival of patients suffering from tumors, including gastric tumors. Members of the GTM gene family can be over-expressed in gastric tumor tissue and other tumor tissue, and thus can be used as markers for gastric and other types of cancer. GTM proteins can be released from cancer cells, and can reach sufficiently high concentrations in the serum and/or other fluids to permit their detection. Thus, methods and test kits for detection and quantification of GTM can provide a valuable tool for diagnosis of gastric cancer.

Claims

1. A method for detecting gastric cancer, comprising:

(a) providing a biological sample; and

(b) detecting over-expression of a GTM family member in said sample.

2. The method of claim 1, wherein said GTM family member is selected from the group consisting of carboxypeptidase N, polypeptide 2, 83 kDa chain (CPN2), matrix metalloproteinase 12 (MMP12), inhibin (“

INHBA”

), insulin-like growth factor 7 (“

IGFBP7”

), gamma-glutamyl hydrolase (“

GGH”

), leucine proline-enriched proteoglycan (“

LEPRE1”

), cystatin S (“

CST4”

), secreted frizzled-related protein 4 (“

SFRP4”

), asporin (“

ASPN”

), cell growth regulator with EF hand domain 1 (“

CGREF1”

), kallikrein 10 (KLK10), tissue inhibitor of metalloproteinase 1 (“

TIMP1”

), secreted acidic cysteine-rich protein (“

SPARC”

), transforming growth factor, β

-induced (“

TGFBI”

), EGF-containing fibulin-like extracellular matrix protein 2 (“

EFEMP2”

), lumican (“

LUM”

), stannin (“

SNN”

), secreted phosphoprotein 1 (“

SPP1”

), chondroitin sulfate proteoglycan 2 (“

CSPG2”

), N-acylsphingosine amidohydrolase (“

ASAH1”

), serine protease 11 (“

PRSS11”

), secreted frizzled-related protein 2 (“

SFRP2”

), phospholipase A2, group XIIB (“

PLA2G12B”

), spondin 2, extracellular matrix protein (“

SPON2”

), olfactomedin 1 (“

OLFM1”

), thrombospondin repeat containing 1 (“

TSRC1”

), thrombospondin 2 (“

THBS2”

), adlican, cystatin SA (“

CST2”

), cystatin SN (“

CST1”

), lysyl oxidase-like enzyme 2 (“

LOXL2”

), thyroglobulin (“

TG”

), transforming growth factor betal (“

TGFB1”

), serine or cysteine proteinase inhibitor clade H (“

SERPINH1”

), serine or cysteine proteinase inhibitor clade B (“

SERPINB5”

), matrix metalloproteinase 2 (“

MMP2”

), proprotein convertase subtilisin/kexin type 5 (“

PCSK5”

) and hyaluronan glycoprotein link protein 4 (“

HAPLN4”

).

3. The method of claim 2, wherein said step of detecting is carried out by detecting over-expression of GTM mRNA.

4. The method of claim 2, wherein said step of detecting is carried out by detecting over-expression of GMT cDNA.

5. The method of claim 4, wherein said step of detecting is carried out using an oligonucleotide complementary to at least a portion of said GMT cDNA.

6. The method of claim 4, wherein said step of detecting is carried out using qPCR method using a fonvard primer and a reverse primer.

7. The method of claim 2, wherein said step of detecting is carried out by detecting over expression of a GTM protein.

8. The method of claim 2, wherein said step of detecting is carried out by detecting over expression of a GTM peptide.

9. The method of claim 8, wherein said step of detecting is carried out using an antibody directed against said GMT.

10. The method of claim 9, wherein said step of detecting is carried out using a sandwich-type immunoassay method.

11. The method of claim 9, wherein said antibody is a monoclonal antibody.

12. The method of claim 9, wherein said antibody is a polyclonal antiserum.

13. A device for detecting a GTM, comprising:

a substrate having a GTM capture reagent thereon; and

a detector associated with said substrate, said detector capable of detecting a GTM associated with said capture reagent.

14. The device of claim 13, wherein said GTM capture reagent is an oligonucleotide.

15. The device of claim 13, wherein said GTM capture reagent is an antibody specific for either a GTM oligonucleotide, a GTM protein or a GTM peptide.

16. A kit for detecting cancer, comprising:

a substrate having a GTM capture reagent thereon;

a means for visualizing a complex of said GMT capture agent and a GMT;

reagents; and

instructions for use.

17. The kit of claim 16, wherein said GTM capture reagent is a GTM-specific oligonucleotide.

18. The kit of claim 16, wherein said GTM capture reagent is a GTM-specific antibody selective for a GTM oligonucleotide, a GTM protein or a GTM peptide.

19. A method for detecting gastric cancer, comprising the steps of:

providing a test sample from a patient suspected of having gastric cancer;

measuring the presence of a GTM protein in said test sample; and

comparing the amount of GTM present in said test sample with a value obtained from a control sample from a subject not having gastric cancer.

21. The method of claim 19, wherein said GTM is a GTM protein or peptide.

22. The method of claim 19, wherein said GTM is an oligonucleotide specific for a GTM.

23. The method of claim 22, wherein said oligonucleotide is DNA.

24. The method of claim 22, wherein said oligonucleotide is RNA.

25. The method of claim 19, wherein said step of measuring uses an ELISA assay.

26. The method of claim 19, wherein said test sample is obtained from plasma.

27. The method of claim 19, wherein said test sample is obtained from tissue, urine, gastric fluid, serum and stool.

20. A method for screening for gastric cancer, comprising the steps of:

providing a test sample from a test subject;

measuring the presence of a GTM in said test sample; and

comparing the amount of GTM present in said test sample with a value obtained from a control sample from a subject not having gastric cancer.