Methods and compositions for diagnosing hepatocellular carcinoma

Abstract

Methods for the diagnosis of hepatocellular carcinoma (HCC) are set forth. Improved assay methods and scanning methods are included that employ non-cell-associated and cell-associated HCC related proteins. Such methods are based upon the discovery of genes that were up-regulated in diseased versus normal tissue as well as in HCC tissue when compared to the tissue of patients with other ailments.

1 . A method of detecting the presence of HCC in a mammal comprising: a) obtaining a biological sample from the mammal; b) assaying the sample to quantify at least a non-cell-associated HCC related protein; and c) comparing the quantity of the non-cell-associated HCC related protein to a control level. 
     
     
         2 . The method of  claim 1  wherein assaying the sample is selected from the group consisting of using an enzyme linked immunosorbent assay (ELISA) and competition assays using monoclonal, polyclonal, or a combination of monoclonal and polyclonal antibodies. 
     
     
         3 . The method of  claim 1 , wherein assaying the sample includes using a receptor molecule that interacts specifically with the non-cell-associated HCC related protein. 
     
     
         4 . The method of  claim 1 , wherein assaying the sample includes an activity assay and the non-cell-associated HCC related protein is selected from the group consisting of an enzyme and involved in a quantifiable chemical or biological reaction. 
     
     
         5 . The method of  claim 2  wherein the polyclonal antibodies include those that bind PLA2G13. 
     
     
         6 . A method of detecting the presence of HCC in a mammal comprising: a) obtaining a tissue sample from the mammal; b) assaying the sample to quantify at least one of a cell-associated HCC related protein; and c) comparing the quantity of cell-associated HCC related proteins to a control level. 
     
     
         7 . The method of  claim 6 , wherein the tissue sample is obtained by biopsy. 
     
     
         8 . The method of  claim 6 , wherein the tissue sample is a liver tissue sample. 
     
     
         9 . The method of  claim 6  wherein assaying the sample is selected from the group consisting of competition assays using monoclonal, polyclonal, or a combination of monoclonal and polyclonal antibodies. 
     
     
         10 . The method of  claim 9  wherein the polyclonal antibodies include those that bind PLA2G13. 
     
     
         11 . A method of detecting HCC in a mammal comprising: a) injecting the mammal with a conjugate including a targeting reagent and an imaging agent; b) imaging the mammal; and c) evaluating the resulting image for the presence of at least one of a cell-associated HCC related protein. 
     
     
         12 . The method of  claim 11 , wherein the targeting agent is selected from at least one of the group consisting of an antibody, a receptor and a ligand and wherein the antibody, receptor and ligand specifically interacts with at least one of the cell-associated HCC related proteins. 
     
     
         13 . The method of  claim 11  wherein the targeting agent is anti-PLA2G13. 
     
     
         14 . The method of  claim 11 , wherein the imaging agent is selected from the group consisting of a dye, radioisotope and a compound that enhances the sensitivity of a scanning methodology selected from the group consisting of magnetic resonance imaging (MRI), ultrasound, computer assisted tomography (CT), single photon emission computer assisted tomography (SPECT) and immunoscintography. 
     
     
         15 . (canceled) 
     
     
         16 . A method of detecting HCC in a mammal comprising: a) obtaining a sample of the mammal's liver tissue; and b) employing at least one of the group consisting of an immunocytochemistry technique using a cell-associated HCC related protein-specific antibody conjugated to at least one imaging agent and an immunohistochemistry technique using a cell-associated HCC related protein-specific antibody conjugated to at least one imaging agent.