Methods of diagnosing endometriosis

Abstract

The present invention provides biomarkers for the diagnosis and prognosis of endometriosis. Generally, the methods of this invention find use in diagnosing or for providing a prognosis for endometriosis by detecting the expression levels of biomarkers, which are differentially expressed (up- or down-regulated) in endometrial cells from a patient with endometriosis. Similarly, these markers can be used to diagnose reduced fertility in a patient with endometriosis or to provide a prognosis for a fertility trial in a patient suffering from endometriosis. The present invention also provides methods of identifying a compound for treating or preventing endometriosis. Finally, the present invention provides kits for the diagnosis or prognosis of endometriosis.

What is claimed is: 
     
         1 . A method for detecting the expression of biomarkers in a biological sample comprising endometrial cells or tissue from a human subject, the method comprising:
 detecting in the biological sample expression of a gene or protein, wherein said gene or protein is selected from the group consisting of:   Oviductal glycoprotein 1 precursor (OVGP1);   Secretoglobin, family 2A, member 2 (SCGB2A2);   Granzyme A (GZMA);   Secreted frizzled-related protein 4 (SFRP4);   Progestagen-associated endometrial protein/Glycodelin (PAEP);   Stanniocalcin 1 (STC1);   Insulin-like growth factor binding protein 1 (IGFBP1);   Complement component 4 binding protein, alpha (C4BPA);   Retinol binding protein 4 (RBP4); and   Olfactomedin 1 (OLFM1).   
     
     
         2 . The method of  claim 1 , wherein protein is detected. 
     
     
         3 . The method of  claim 1 , wherein RNA expression is detected. 
     
     
         4 . The method of  claim 1 , wherein the sample comprises early secretory phase, mid secretory phase, or proliferative phase endometrial cells or tissue. 
     
     
         5 . The method of  claim 1 , wherein the gene or protein is selected from Secretoglobin, family 2A, member 2 (SCGB2A2), Secreted frizzled-related protein 4 (SFRP4), Progestagen-associated endometrial protein/Glycodelin (PAEP), Stanniocalcin 1 (STC1), or Olfactomedin 1 (OLFM1), and the sample comprises early secretory phase endometrial cells or tissue. 
     
     
         6 . The method of  claim 1 , wherein the gene or protein is selected from Secretoglobin, family 2A, member 2 (SCGB2A2), Granzyme A (GZMA), Insulin-like growth factor binding protein 1 (IGFBP1), Complement component 4 binding protein, alpha (C4BPA), or Retinol binding protein 4 (RBP4), and the sample comprises mid secretory phase endometrial cells or tissue. 
     
     
         7 . The method of  claim 1 , wherein the gene or protein is Oviductal glycoprotein 1 precursor (OVGP1), and the sample comprises proliferative phase endometrial cells or tissue. 
     
     
         8 . The method of  claim 1 , further comprising:
 (i) detecting altered expression (over or under expression) of the gene or protein in the sample, wherein said altered expression is selected from the group consisting of:   under expression of Oviductal glycoprotein 1 precursor (OVGP1);   under expression of Secretoglobin, family 2A, member 2 (SCGB2A2);   over expression of Granzyme A (GZMA);   over expression of Secreted frizzled-related protein 4 (SFRP4);   under expression of Progestagen-associated endometrial protein/Glycodelin (PAEP);   under expression of Stanniocalcin 1 (STC1);   under expression of Insulin-like growth factor binding protein 1 (IGFBP1);   over expression of Complement component 4 binding protein, alpha (C4BPA);   under expression of Retinol binding protein 4 (RBP4); and   over expression of Olfactomedin 1 (OLFM1).   
     
     
         9 . The method of  claim 8 , wherein the altered expression is selected from the under expression of Secretoglobin, family 2A, member 2 (SCGB2A2), over expression of Secreted frizzled-related protein 4 (SFRP4), under expression of Progestagen-associated endometrial protein/Glycodelin (PAEP), under expression of Stanniocalcin 1 (STC1), and over expression of Olfactomedin 1 (OLFM1) gene or protein, and the sample comprises early secretory phase endometrial cells or tissue. 
     
     
         10 . The method of  claim 8 , wherein the altered expression is selected from the under expression of Secretoglobin, family 2A, member 2 (SCGB2A2), over expression of Granzyme A (GZMA), under expression of Insulin-like growth factor binding protein 1 (IGFBP1), over expression of Complement component 4 binding protein, alpha (C4BPA), and under expression of Retinol binding protein 4 (RBP4) gene or protein, and the sample comprises mid secretory phase endometrial cells or tissue. 
     
     
         11 . The method of  claim 8 , wherein the altered expression is selected from under expression of Oviductal glycoprotein 1 precursor (OVGP1) gene or protein, and the sample comprises proliferative phase endometrial cells or tissue. 
     
     
         12 . The method of  claim 8 , wherein over or under expression of at least 50% compared to a baseline value representative of expression in a sample from a human subject without endometriosis provides a diagnosis or prognosis for endometriosis. 
     
     
         13 . A method of treating endometriosis in a subject suffering from endometriosis, the method comprising detecting the expression of biomarkers in a biological sample comprising endometrial cells or tissue from a human subject as in  claim 1 , and treating the endometriosis if the biomarkers are over or under expressed by at least 50% compared to a baseline value representative of expression in a sample from a human subject without endometriosis. 
     
     
         14 . The method of  claim 13 , wherein the treating comprises pain killers, hormonal treatments, chemotherapy, or surgical treatments. 
     
     
         15 . A method of identifying a compound for treating or preventing endometriosis, the method comprising the steps of: contacting a compound with a cell expressing a protein selected from the group consisting of Oviductal glycoprotein 1 precursor (OVGP1); Secretoglobin, family 2A, member 2 (SCGB2A2); Granzyme A (GZMA); Secreted frizzled-related protein 4 (SFRP4); Progestagen-associated endometrial protein/Glycodelin (PAEP); Stanniocalcin 1 (STC1); Insulin-like growth factor binding protein 1 (IGFBP1); Complement component 4 binding protein, alpha (C4BPA); Retinol binding protein 4 (RBP4); and Olfactomedin 1 (OLFM1), and detecting altered expression of the protein as compared to a control, thereby identifying the compound. 
     
     
         16 . A kit for diagnosing endometriosis, comprising a probe for one or more nucleic acid biomarkers selected from the group consisting of Oviductal glycoprotein 1 precursor (OVGP1); Secretoglobin, family 2A, member 2 (SCGB2A2); Granzyme A (GZMA); Secreted frizzled-related protein 4 (SFRP4); Progestagen-associated endometrial protein/Glycodelin (PAEP); Stanniocalcin 1 (STC1); Insulin-like growth factor binding protein 1 (IGFBP1); Complement component 4 binding protein, alpha (C4BPA); Retinol binding protein 4 (RBP4); and Olfactomedin 1 (OLFM1).