Tumor markers in ovarian cancer

Abstract

The present invention features methods of diagnosing and prognosticating ovarian tumors by detecting increased expression of an ovarian tumor marker gene in a subject or in a sample from a subject. Also featured are kits for the aforementioned diagnostic and prognostic methods. In addition, the invention features methods of treating and preventing ovarian tumors, and methods of inhibiting the growth or metastasis of ovarian tumors, by modulating the production or activity of an ovarian tumor marker polypeptide. Further featured are methods of inhibiting the growth or metastasis of an ovarian tumor by contacting an ovarian tumor cell with an antibody that specifically binds an ovarian tumor marker polypeptide.

1 . A method of detecting an ovarian tumor in a subject, said method comprising measuring the expression level of an ovarian tumor marker gene in said subject, wherein an increase in said expression level of said ovarian tumor marker gene in said subject, relative to the expression level of said ovarian tumor marker gene in a reference subject not having an ovarian tumor, detects an ovarian tumor in said subject. 
     
     
         2 . A method of identifying a subject at increased risk for developing ovarian cancer, said method comprising measuring the expression level of an ovarian tumor marker gene in said subject, wherein an increase in said expression level of said ovarian tumor marker gene in said subject, relative to the expression level of said ovarian tumor marker gene in a reference subject not at increased risk for developing ovarian cancer, identifies an individual at increased risk for developing ovarian cancer. 
     
     
         3 . The method of  claim 1  or  2 , wherein said expression level of said ovarian tumor marker gene is determined in said subject by measuring the expression level of said tumor marker gene in a sample from said subject. 
     
     
         4 . The method of  claim 3 , wherein said sample from said subject is selected from the group consisting of a tissue biopsy, ovarian epithelial cell scrapings, peritoneal fluid, blood, urine, and serum. 
     
     
         5 . The method of  claim 1  or  2 , wherein said expression level of said tumor marker gene is measured in vivo in said subject. 
     
     
         6 . The method of  claim 1  or  2 , wherein said expression level of said tumor marker gene is determined by measuring the level of ovarian tumor marker mRNA. 
     
     
         7 . The method of  claim 6 , wherein said level of ovarian tumor marker mRNA is measured using RT-PCR, Northern hybridization, dot-blotting, or in situ hybridization. 
     
     
         8 . The method of  claim 1  or  2 , wherein said expression level of said ovarian tumor marker gene is determined by measuring the level of ovarian tumor marker polypeptide encoded by said ovarian tumor marker gene. 
     
     
         9 . The method of  claim 8 , wherein said level of ovarian tumor marker polypeptide is measured by ELISA, immunoblotting, or immunohistochemistry. 
     
     
         10 . The method of  claim 1  or  2 , wherein said expression level of said tumor marker gene is compared to the expression level of said tumor marker gene in a reference subject diagnosed with ovarian cancer. 
     
     
         11 . The method of  claim 2 , wherein said expression level of said ovarian tumor marker gene in said subject is compared to the expression level of said tumor marker gene in a reference subject that is identified as having an increased risk for developing ovarian cancer. 
     
     
         12 . A method of identifying a tumor as an ovarian tumor, said method comprising measuring the expression level of an ovarian tumor marker gene in a tumor cell from said tumor, wherein an increase in said expression level of said ovarian tumor marker gene in said tumor cell, relative to the expression level of said ovarian tumor marker gene in a noncancerous ovarian cell, identifies the tumor as an ovarian tumor. 
     
     
         13 . A method of treating or preventing an ovarian tumor in a subject, said method comprising modulating production or activity of a polypeptide encoded by an ovarian tumor marker gene in an ovarian epithelial cell in said subject. 
     
     
         14 . A method of inhibiting the growth or metastasis of an ovarian tumor in a subject, said method comprising contacting an ovarian tumor cell with an antibody that specifically binds an ovarian tumor marker polypeptide encoded by an ovarian tumor marker gene, wherein the binding of said antibody to said ovarian tumor marker polypeptide inhibits the growth or metastasis of said ovarian tumor in said subject. 
     
     
         15 . The method of  claim 14 , wherein said ovarian tumor marker polypeptide is on the surface of said ovarian tumor cell. 
     
     
         16 . The method of  claim 14 , wherein said antibody is coupled to a radioisotope or a toxic compound. 
     
     
         17 . A method of diagnosing ovarian cancer in a subject, said method comprising measuring the amount of an ovarian tumor marker polypeptide in said subject, wherein an amount of ovarian tumor marker polypeptide that is greater than the amount of ovarian tumor marker polypeptide measured in a subject not having ovarian cancer diagnoses an ovarian cancer in the subject. 
     
     
         18 . The method of  claim 17 , wherein said ovarian tumor marker polypeptide is present at the surface of a cell. 
     
     
         19 . The method of  claim 17 , wherein said ovarian tumor marker polypeptide is in soluble form. 
     
     
         20 . The method of  claim 1 ,  2 ,  12 ,  13 ,  14 , or  17 , wherein said ovarian tumor marker gene is selected from the group consisting of HLA-DR alpha chain; cysteine-rich protein 1; claudin 4; claudin 3; ceruloplastnin (ferroxidase); gluthathione perroxidase 3; secretory leukocyte protease inhibitor; HOST-1 (FLJ14303 fis); interferon-induced transmembrane protein 1; apolipoprotein J/clusterin; serine protease inhibitor, Kunitz type 2; apoplipoprotein E; complement component 1, r subcomponent; G1P3/IFI-6-16; Lutheran blood group (BCAM); collagen type III, alpha-1; Mal (T cell differentiation protein); collagen type I, alpha-2; HLA-DPB1; bone marrow stroma antigen 2 (BST-2); or HLA-Cw. 
     
     
         21 . The method of  claim 1 ,  2 ,  12 ,  13 ,  14 , or  17 , wherein said ovarian tumor is an epithelial ovarian tumor. 
     
     
         22 . The method of  claim 21 , wherein said epithelial ovarian tumor is selected from the group consisting of a serous cystadenoma, a borderline serous tumor, a serous cystadenocarcinoma, a mucinous cystadenoma, a borderline mucinous tumor, a mucinous cystadenocarcinoma, an endometrioid carcinoma, an undifferentiated carcinoma, a clear cell adenocarcinoma, a cystadenofibroma, an adenofibroma, and a Brenner tumor. 
     
     
         23 . A kit comprising an antibody for measuring the expression level of an ovarian tumor marker gene in a subject. 
     
     
         24 . A kit comprising a nucleic acid for measuring the expression level of an ovarian tumor marker gene in a subject. 
     
     
         25 . The kit of  claim 23  or  24 , wherein said ovarian tumor marker gene is selected from the group consisting of HLA-DR alpha chain; cysteine-rich protein 1; claudin 4; claudin 3; ceruloplasmin (ferroxidase); glutathione perroxidase 3; secretory leukocyte protease inhibitor; HOST-1 (FLJ14303 fis); interferon-induced transmembrane protein 1; apolipoprotein J/clusterin; serine protease inhibitor, Kunitz type 2; apoplipoprotein E; complement component 1, r subcomponent; G1P3/IFI-6-16; Lutheran blood group (BCAM); collagen type III, alpha-1; Mal (T cell differentiation protein); collagen type I, alpha-2; HLA-DPB1; bone marrow stroma antigen 2 (BST-2); or HLA-Cw.