Nuclear matrix protein alterations associated with colon cancer and colon metastasis to the liver, and uses thereof

Abstract

Proteins useful in the diagnosis of proliferative disorders of the colon are present in nuclear matrix protein preparations and can be characterized by molecular weight, isoelectric point, and amino acid sequence. The proteins may be identified, for example, by 2D-gel electrophoresis or by specific binding partners, such as antibodies.

1 . A method of diagnosing a proliferative disorder of the colon in a patient, comprising analyzing colon tissue, stool, or a body fluid from the patient for the presence of a CC4 polypeptide that comprises Ile-Leu-Leu-Phe-Asp-Tyr-Phe-Asn-Arg (SEQ ID NO: 28) and that has a molecular weight of 43 kD and a pI of 6.22, wherein the presence of the polypeptide is indicative of a proliferative disorder of the colon. 
     
     
         2 . The method of  claim 1 , wherein the polypeptide further comprises SEQ ID NOS: 27 and 29. 
     
     
         3 . The method of  claim 1 , wherein the presence of the polypeptide is determined using an antibody that specifically binds to the protein. 
     
     
         4 . The method of  claim 3 , wherein the antibody is a monoclonal antibody. 
     
     
         5 . The method of  claim 3 , wherein the antibody is a polyclonal antibody. 
     
     
         6 . The method of  claim 1 , wherein said analyzing comprises:
 (a) contacting the colon tissue, stool, or body fluid with an antibody that specifically binds the CC4 polypeptide; and then   (b) determining whether the CC4 polypeptide is present based on the antibody binding.   
     
     
         7 . The method of  claim 1 , wherein the proliferative disorder of the colon is a malignant disorder of the colon. 
     
     
         8 . The method of  claim 7 , wherein the malignant disorder of the colon is colon adenocarcinoma. 
     
     
         9 . The method of  claim 1 , wherein the method comprises analyzing colon tissue from the patient. 
     
     
         10 . The method of  claim 1 , wherein the method comprises analyzing a body fluid from the patient. 
     
     
         11 . The method of  claim 10 , wherein the body fluid is serum. 
     
     
         12 . The method of  claim 1 , wherein the method comprises analyzing stool from the patient. 
     
     
         13 . A method of diagnosing a colon cancer in a patient, comprising analyzing tissue from the patient's colon, stool from the patient, or a body fluid from the patient for the presence of CC4 comprising SEQ ID NO: 28 and having a molecular weight of 43 kD and a pI of 6.22, wherein the presence of CC4 is indicative of colon cancer. 
     
     
         14 . The method of  claim 13 , wherein the presence of CC4 is determined using an antibody that specifically binds to the protein. 
     
     
         15 . A method for diagnosing a patient with a colon adenocarcinoma, comprising:
 (a) acquiring a sample of suspect colonic tissue from the patient, stool from the patient, or a body fluid from the patient;   (b) measuring the level of a CC4 polypeptide comprising the amino acid sequence of SEQ ID NO: 28 and having a molecular weight of 43 kD and a pI of 6.22 in the sample by contacting the sample with an antibody that specifically binds to said polypeptide; and   (c) comparing the determined level of the polypeptide in the sample with the level of the polypeptide in a sample of normal colonic tissue or body fluid,   
       wherein a level of the polypeptide that is greater in the patient sample as compared to the level of the polypeptide in the normal colonic tissue or body fluid is indicative of colon adenocarcinoma.