Annexin proteins and autoantibodies as serum markers for cancer

Abstract

The present invention relates to screening methods for diagnosis, prognosis, or susceptibility to cancer in a subject by means of detecting the presence of serum autoantibodies to specific annexin protein antigens in sera from subjects. The present invention also provides screening methods for diagnosis and prognosis of cancer in a subject by means of detecting increased expression levels of annexin proteins in biological samples of the subject. The method of the invention can also be used to identify subjects at risk for developing cancer. The method of the invention involves the use of subject derived biological samples to determine the occurrence and level of expression of annexin proteins or expression of annexin derived peptides or antigens, and/or the occurrence and level of circulating autoantibodies to specific annexin protein antigens. The present invention further provides for kits for carrying out the above described screening methods. Such kits can be used to screen subjects for increased levels of annexin proteins, or for the detection of autoantibodies to annexin proteins, as a diagnostic, predictive or prognostic indicator of cancer.

We claim:  
     
         1 . A method for diagnosis and prognosis of cancer in a subject comprising: 
 (a) quantitatively detecting annexin protein in a biological sample derived from a subject; and    (b) comparing the level of protein detected in the subject's sample to the level of protein detected in a control sample,    wherein an increase in the level of annexin protein detected in the subject's sample as compared to a control sample is an indicator of a subject with cancer.    
     
     
         2 . The method of  claim 1  wherein the annexin protein is detected using an immunoassay.  
     
     
         3 . The method of  claim 2  wherein the immunoassay is an immunoprecipitation assay.  
     
     
         4 . The method of  claim 1  wherein the sample is a lung tissue sample.  
     
     
         5 . The method of  claim 1  wherein the cancer is lung cancer.  
     
     
         6 . A method for diagnosis of a subject with cancer comprising: 
 (a) contacting an antibody containing biological sample derived from a subject with a sample containing annexin protein antigens under conditions such that an immunospecific antigen-antibody binding reaction can occur; and    (b) detecting immunospecific binding of the autoantibodies to the annexin protein in the subject's biological sample,    wherein the presence of autoantibodies indicates the presence of cancer in the subject.    
     
     
         7 . The method of  claim 6  wherein the step of detecting the autoantibodies in the subject's biological sample comprises the use of a signal-generating component bound to an antibody that is specific for antibodies in the subject's biological sample.  
     
     
         8 . The method of  claim 7  wherein the presence of autoantibodies in the biological sample is measured by an immunoassay comprising: 
 (a) immobilizing one or more annexin protein onto a membrane or substrate;  
 (b) contacting the membrane or substrate with a subject's biological sample; and  
 (c) detecting the presence of autoantibodies specific for the annexin protein in the subject's biological sample,  
 wherein the presence of autoantibodies indicates the presence of cancer.  
 
     
     
         9 . The method of  claim 6  wherein the cancer is lung cancer.  
     
     
         10 . A kit for diagnosis and prognosis of cancer in a subject comprising a component for detecting the presence of annexin protein in a biological sample.  
     
     
         11 . The kit of  claim 10  wherein the component for detecting annexin protein is an anti-annexin antibody.  
     
     
         12 . The kit of  claim 11  wherein the anti-annexin antibody is labeled.  
     
     
         13 . The kit of  claim 12  wherein the label is radioactive, fluorescent, colorimeter or enzyme label.  
     
     
         14 . The kit of  claim 11  further comprising a labeled second antibody that immunospecifically binds to the anti-annexin antibody.  
     
     
         15 . A kit for diagnosis and prognosis of cancer in a subject comprising a component for detecting the presence of annexin autoantibodies in a sample.  
     
     
         16 . The kit of  claim 15  wherein the component is an annexin antigen.  
     
     
         17 . The kit of  claim 16  wherein the annexin antigen is labeled.  
     
     
         18 . The kit of  claim 16  wherein the annexin antigen is linked to a solid phase.  
     
     
         19 . The kit of  claim 15  further comprising a component for detection of the annexin autoantibody.