Pro-angiogenic genes in ovarian tumor endothelial cell isolates

Abstract

A gene profiling signature for ovarian tumor endothelial cells is disclosed herein. The gene signature can be used to diagnosis or prognosis an ovarian tumor, identify agents to treat an ovarian tumor, to predict the metastatic potential of an ovarian tumor and to determine the effectiveness of ovarian tumor treatments. Thus, methods are provided for identifying agents that can be used to treat ovarian cancer, for determining the effectiveness of an ovarian tumor treatment, or to diagnose or prognose an ovarian tumor. Methods of treatment are also disclosed which include administering a composition that includes a specific binding agent that specifically binds to one of the disclosed ovarian endothelial cell tumor-associated molecules and inhibits ovarian tumor in the subject.

We claim: 
     
         1 . A method of diagnosing an epithelial ovarian tumor with a poor prognosis in a subject, comprising:
 contacting a sample containing ovarian tissue, ovarian cells or ovarian endothelial cells obtained from the subject with the epithelial ovarian tumor with at least wild-type JAGGED1 nucleic acid molecule or an anti-wild-type JAGGED1 antibody; comparing expression of at least wild-type JAGGED1 detected in the sample obtained from the subject with the epithelial ovarian tumor to a control; and detecting an at least 2-fold increase in expression of wild-type JAGGED1 relative to a control indicates the subject has a poor prognosis, thereby diagnosing the epithelial ovarian tumor in a subject with a poor prognosis.   
     
     
         2 . The method of  claim 1 , wherein an at least 2-fold increase in expression of wild-type JAGGED1 as compared to the control indicates a stage III or stage IV epithelial ovarian tumor. 
     
     
         3 . The method of  claim 1 , wherein an at least 2-fold increase in expression of wild-type JAGGED1 as compared to the control indicates a high grade epithelial ovarian tumor. 
     
     
         4 . The method of  claim 1 , wherein expression of wild-type JAGGED1 is determined by polymerase chain reaction. 
     
     
         5 . The method of  claim 1 , further comprising treating the subject with the epithelial ovarian tumor with a poor prognosis by administering to the subject an effective amount of at least one specific binding agent, wherein at least one of the at least one specific binding agents preferentially binds to wild-type JAGGED1 and inhibits epithelial ovarian tumor growth in the subject, wherein the specific binding agent that preferentially binds to wild-type JAGGED1 is a wild-type JAGGED1 siRNA. 
     
     
         6 . The method of  claim 1 , wherein the control is a sample obtained from a subject that has a non-metastatic ovarian tumor. 
     
     
         7 . The method of  claim 1 , wherein the wild-type JAGGED 1 nucleic acid molecule or an anti-wild-type JAGGED1 antibody is positioned on an addressable array. 
     
     
         8 . The method of  claim 1 , further comprising contacting a sample containing ovarian tissue, ovarian cells or ovarian endothelial cells obtained from the subject with the epithelial ovarian tumor with wild-type Zeste homologue 2 (EZH2) nucleic acid molecule or an anti-wild-type EZH2 antibody; comparing expression of at least wild-type EZH2 detected in the sample obtained from the subject with the epithelial ovarian tumor to a control; and detecting an at least 2-fold increase in expression of wild-type EZH2 relative to a control indicates the subject has a poor prognosis, thereby diagnosing the epithelial ovarian tumor in a subject with a poor prognosis. 
     
     
         9 . The method of  claim 1 , further comprising contacting a sample containing ovarian tissue, ovarian cells or ovarian endothelial cells obtained from the subject with the epithelial ovarian tumor with wild-type protein tyrosine kinase 2 (PTK2) nucleic acid molecule or an anti-wild-type PTK2 antibody; comparing expression of at least wild-type PTK2 detected in the sample obtained from the subject with the epithelial ovarian tumor to a control; and detecting an at least 2-fold increase in expression of wild-type PTK2 relative to a control indicates the subject has a poor prognosis, thereby diagnosing the epithelial ovarian tumor in a subject with a poor prognosis. 
     
     
         10 . The method of  claim 1 , further comprising contacting a sample containing ovarian tissue, ovarian cells or ovarian endothelial cells obtained from the subject with the epithelial ovarian tumor with wild-type Zeste homologue 2 (EZH2) nucleic acid molecule, an anti-wild-type EZH2 antibody, a wild-type protein tyrosine kinase 2 (PTK2) nucleic acid molecule, or an anti-wild type PTK2 antibody; comparing expression of at least wild-type EZH2 and/or wild-type PTK2 detected in the sample obtained from the subject with the epithelial ovarian tumor to a control; and detecting an at least 2-fold increase in expression of wild-type EZH2 and/or wild-type PTK2 relative to a control indicates the subject has a poor prognosis, thereby diagnosing the epithelial ovarian tumor in a subject with a poor prognosis. 
     
     
         11 . The method of  claim 5 , wherein the at least one specific binding agent further comprises a specific binding agent that preferentially binds to wild-type EZH2 and is a wild-type EZH2 siRNA. 
     
     
         12 . The method of  claim 5 , wherein the at least one specific binding agent further comprises a specific binding agent that preferentially binds to wild-type PTK2 and is a wild-type PTK2 siRNA. 
     
     
         13 . The method of  claim 5 , wherein the at least one specific binding agent further comprises a specific binding that preferentially binds to wild-type PTK2 which is a wild-type PTK2 siRNA and/or a specific binding agent that preferentially binds to wild-type EZH2 which is a wild-type EZH2 siRNA.