Biomarkers for early detection of ovarian cancer

Abstract

Biomarker proteins that can be used in the diagnosis of early-stage ovarian cancer (OC) are described. The biomarker panels not only permit the distinction of patients with ovarian neoplasia (benign or malignant) from normal subjects, but they also allow the identification of patients with early-stage (stage I/II) ovarian cancer from those patients with benign ovarian tumors or normal individuals. The invention additionally provides methods for detecting and treating various cancers, including cancer of the ovary using OC-related molecules.

1 - 10 . (canceled) 
     
     
         11 . A method of screening for status of ovarian neoplasia in a subject comprising:
 (a) measuring by immunoassay three biomarkers consisting of transthyretin, apolipoprotein AI (ApoAI) and transferrin in a tissue sample of the subject,   (b) comparing the measured three biomarkers of the sample to a measurement of the three biomarkers in normal tissue, and   (c) detecting a decrease in the measured three biomarkers of the sample compared to the measurement of the three biomarkers in normal, thereby identifying the subject as having ovarian neoplasia.   
     
     
         12 . The method of  claim 11 , further comprising measuring CA125. 
     
     
         13 . The method of  claim 11 , wherein the sample comprises serum. 
     
     
         14 . The method of  claim 11 , wherein the immunoassay comprises enzyme-linked immunosorbent assay (ELISA), enzyme-linked immunofluoresent assay (ELIFA), Western blot, radioimmunoassay, or slot blot. 
     
     
         15 . A method of determining the status of ovarian neoplasia in a sample of serum obtained from a subject, the method comprising:
 (a) contacting the serum sample with:
 (i) an antibody that specifically binds transthyretin; 
 (ii) an antibody that specifically binds transferrin; and 
 (iii) an antibody that specifically binds apolipoprotein AI (ApoAI). 
   (b) measuring the binding of the antibodies (i)-(iii) to the biomarkers;   (c) comparing the binding to a control sample; and   (d) determining the status of neoplasia to be malignant if the binding of the antibodies to transthyretin, transferrin and/or ApoAI is reduced in the serum sample from the subject relative to the control sample.   
     
     
         16 . The method of  claim 15 , further comprising contacting the serum sample with an antibody that binds CA125, wherein increased binding of the antibody to CA125 in the serum sample obtained from the subject relative to the control sample is indicative of neoplasia. 
     
     
         17 . The method of  claim 15 , wherein the antibodies are bound to a substrate. 
     
     
         18 . The method of  claim 15 , wherein the antibody is labeled with a detectable marker. 
     
     
         19 . The method of  claim 15 , further comprising initiating or continuing treatment of the subject with a therapeutic regimen directed against ovarian cancer when the status of ovarian neoplasia is determined to be malignant. 
     
     
         20 . A method of detecting ovarian neoplasia in a sample of serum obtained from a subject, the method comprising:
 (a) contacting the serum sample with:
 (i) an antibody that specifically binds transthyretin; 
 (ii) an antibody that specifically binds transferrin; and 
 (iii) an antibody that specifically binds apolipoprotein AI (ApoAI). 
   (b) measuring the binding of the antibodies (i)-(iii) to the biomarkers;   (c) comparing the binding to a control sample; and   (d) detecting ovarian neoplasia if the binding of the antibodies to transthyretin, transferrin and/or ApoAI is reduced in the serum sample from the subject relative to the control sample.   
     
     
         21 . The method of  claim 20 , further comprising contacting the serum sample with an antibody that binds CA125, wherein increased binding of the antibody to CA125 in the serum sample obtained from the subject relative to the control sample is indicative of neoplasia. 
     
     
         22 . The method of  claim 20 , wherein the antibodies are bound to a substrate. 
     
     
         23 . The method of  claim 20 , wherein the antibody is labeled with a detectable marker. 
     
     
         24 . The method of  claim 20 , wherein ovarian neoplasia is detected with a sensitivity and specificity of at least 80%. 
     
     
         25 . The method of  claim 20 , wherein ovarian neoplasia is detected when the binding of the antibodies is reduced by at least 25%. 
     
     
         26 . The method of  claim 20 , wherein ovarian neoplasia is detected when the binding of the antibodies is reduced by a statistically significant amount. 
     
     
         27 . The method of  claim 20 , wherein the antibody of (i) is a rabbit anti-transthyretin antibody, the antibody of (ii) is a goat anti-sero-transferrin antibody, and the antibody of (iii) is a goat anti-ApoAI antibody. 
     
     
         28 . The method of  claim 20 , wherein the measuring of (b) comprises enzyme-linked immunosorbent assay (ELISA), enzyme-linked immunofluoresent assay (ELIFA), Western blot, radioimmunoassay, or slot blot. 
     
     
         29 . The method of  claim 20 , further comprising initiating or continuing treatment of the subject with a therapeutic regimen directed against ovarian cancer when ovarian neoplasia is detected.