Blood markers for diagnosing epithelium derived cancers and monoclonal antibodies thereof
The present invention provides uses of cytokeratins as markers for diagnosing epithelium derived cancers. The present invention provides cancer-related epitopes of cytokeratins and monoclonal antibodies which specifically recognize the epitopes. The present invention also provides methods for the early screen, diagnosis or prognosis of epithelium derived cancers in subjects, methods for the evaluation of therapeutic effect of related medicaments or therapies, and kits for accomplishing the methods.
1. A monoclonal antibody that specifically binds to an epithelium-derived cancer-related cytokeratin fragment, wherein the fragment comprises one or more epitopes selected from the group consisting of SEQ ID NOs: 2 and 3, wherein the antibody is produced by a hybridoma having a deposit number selected from the group consisting of CGMCC 1957 and CGMCC 1956.
2. The monoclonal antibody of claim 1 , wherein the epithelium-derived cancer-related cytokeratin fragment comprises amino acid residues selected from the group consisting of amino acid residues 1-250 of SEQ ID NO: 1, amino acid residues 250-430 of SEQ ID NO: 1, and amino acid residues 150-430 of SEQ ID NO: 1.
3. The monoclonal antibody of claim 1 , wherein the antibody comprises a chimeric antibody or a humanized antibody.
4. The monoclonal antibody of claim 1 , wherein the epithelium-derived cancer-related cytokeratin fragment is associated with breast cancer, gastric cancer, oral cancer, esophageal cancer, colon cancer, liver cancer, bladder cancer, pancreatic cancer, ovarian cancer, cervical cancer, lung cancer, breast cancer, skin cancer, prostate cancer, or renal cancer.
5. A method of determining a diagnosis or prognosis of cancer in a subject, comprising contacting a biological sample from the subject with a monoclonal antibody that specifically binds to an epithelium-derived cancer-related cytokeratin fragment, wherein the fragment comprises one or more epitopes selected from the group consisting of SEQ ID NOs: 2 and 3, and wherein the antibody is produced by a hybridoma having a deposit number selected from the group consisting of CGMCC 1957 and CGMCC 1956.
6. The method of claim 5 , wherein the epithelium-derived cancer-related cytokeratin fragment comprises amino acid residues selected from the group consisting of amino acid residues 1-250 of SEQ ID NO: 1, amino acid residues 250-430 of SEQ ID NO: 1, and amino acid residues 150-430 of SEQ ID NO: 1.
7. The method of claim 5 , wherein the antibody comprises a chimeric antibody or a humanized antibody.
8. The method of claim 5 , wherein the biological sample comprises blood, serum, tissue fluid, urine, excrement, sputum, cerebrospinal fluid, saliva, tears, or nipple aspirate fluid.
9. The method of claim 5 , wherein the epithelium-derived cancer-related cytokeratin fragment is associated with breast cancer, gastric cancer, oral cancer, esophageal cancer, colon cancer, liver cancer, bladder cancer, pancreatic cancer, ovarian cancer, cervical cancer, lung cancer, breast cancer, skin cancer, prostate cancer, or renal cancer.
10. The method of claim 5 , further comprising comparing the level of a subject's cytokeratin fragments to that of one or more other epithelium-derived tumor markers, wherein the other epithelium-derived tumor markers are selected from the group consisting of AFP, CEA, CA242, CA19-9, CA72-4, CA125, CA15-3, NSE, SCCA, Cyfra21-1, PSA, and free PSA.
11. The method of claim 5 , further comprising contacting the sample with a monoclonal antibody produced by a hybridoma having a deposit number selected from the group consisting of CGMCC 1955 and CGMCC 1952.
12. A kit for determining a diagnosis or prognosis of cancer, comprising the monoclonal antibody of claim 1 .
13. The kit of claim 12 , wherein the epithelium-derived cancer-related cytokeratin fragment comprises amino acid residues selected from the group consisting of amino acid residues 1-250 of SEQ ID NO: 1, amino acid residues 250-430 of SEQ ID NO: 1, and amino acid residues 150-430 of SEQ ID NO: 1.
14. The kit of claim 12 , wherein the monoclonal antibody comprises a chimeric antibody or a humanized antibody.
15. The kit of claim 12 , further comprising an antibody produced by a hybridoma having a deposit number selected from the group consisting of CGMCC 1955 and CGMCC 1952.
16. A hybridoma cell line having a deposit number selected from the group consisting of CGMCC 1957 and CGMCC 1956.