Protein markers for the diagnosis and prognosis of ovarian and breast cancer

Abstract

Plasma samples of ovarian and breast cancer patients were used to search for markers of cancer, using two-dimensional gel electrophoresis and MALDI TOF mass spectrometry. Truncated forms of cytosolic serine hydroxymethyl transferase (cSHMT), T-box transcription factor 3 (Tbx3) and utrophin were aberrantly expressed in samples from cancer patients, as compared to samples from noncancer cases. Aberrant expression of proteins was validated by immunoblotting of plasma samples with specific antibodies to cSHMT, Tbx3 and utrophin. A cohort of 79 breast and 39 ovarian cancer patients, and 31 individuals who were either healthy or had noncancerous conditions was studied. We observed increased expression of truncated cSHMT, Tbx3 and utrophin in plasma samples obtained from patients at early stages of disease. The results indicate that cSHMT, Tbx3, utrophin and truncated forms thereof can be used as components of multiparameter monitoring of ovarian and breast cancer.

1 . (canceled) 
     
     
         2 . A protein marker selected from the group consisting of cSHMT, Tbx3, utrophin and a truncated form of any one of these proteins. 
     
     
         3 . An antibody raised against, a protein selected from the group consisting of cSHMT, Tbx3, utrophin and a truncated form of any one of these proteins. 
     
     
         4 . A kit for the diagnosis of ovarian and/or breast cancer comprising one or more antibodies raised against protein markers selected from cSHMT, Tbx3, utrophin and truncated forms of any of these markers. 
     
     
         5 . A kit for the prognosis of ovarian and/or breast cancer comprising one or more antibodies raised against protein markers selected from cSHMT, Tbx3, utrophin and truncated forms of any of these markers. 
     
     
         6 - 8 . (canceled) 
     
     
         9 . A microarray of proteins and other markers for use in the diagnosis and/or prognosis of ovarian and/or breast cancer which comprises one or more markers selected from cSHMT, Thx3, utrophin and truncated forms thereof in combination with one or more previously known markers. 
     
     
         10 . The microarray according to  claim 9  wherein the one or more previously known markers are selected from the group consisting of CA125, CA15-3, CEA, RS/DJ1, apolipoprotein A1, transthyretin, inter-α trypsin inhibitor heavy chain H4, haptoglobin-1, kallikrein, lysophosphatidic acid, DNA, ErbB2/neu and Ki-67. 
     
     
         11 . The kit according to  claim 4 , wherein the kit is used to test a plasma sample obtained from a patient for the presence and amount of one or more of the markers and wherein
 1) observation of aberrant levels of one or more of the markers identifies the patient as likely having ovarian and/or breast cancer or   2) observation of normal or no expression of the markers identifies the patient as free of those cancers.   
     
     
         12 . The kit according to  claim 5 , wherein the kit is used to test a plasma sample obtained from a patient for the presence and amount of one or more of the markers and wherein the amounts of aberrant levels of any or all of the markers are used for determining the optimal treatment regimen for the patient, for predicting the patient's response to the treatment and for predicting the likelihood of duration of survival of the patient.