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.

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         10 . A method of diagnosing or providing a prognosis of endometriosis, the method comprising the steps of:
 (i) obtaining a biological sample from a human subject suspected of or having endometriosis,   (ii) detecting in the biological sample altered expression (over or under expression of at least 50% compared to a subject without endometriosis) of a gene or protein, wherein said altered expression is selected from the group consisting of:   over expression of Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3B (APOBEC3B);   under expression of DEAD (Asp-Glu-Ala-Asp) box polypeptide (DEAD/H);   over expression of Fibrillin 1 (FBN1);   under expression of Major histocompatibility complex, class II, DOB (HLA-DOB);   over expression of Lactotransferrin (LTF);   under expression of Orosomucoid 2 (ORM2);   under expression of Phospholipase C, beta 4 (PLCB4);   under expression of POM (POM121 homolog, rat) and ZP3 fusion (POMZP3);   under expression of Phosphatidic acid phosphatase, type 2B (PPAP2B); and   under expression of Solute carrier family 15, member 2 (SLC15A2);   wherein altered expression of over or under expression of at least 50% compared to a baseline value representative of expression in a human subject without endometriosis provides a diagnosis or prognosis of endometriosis; and   (iii) providing the diagnosis or the prognosis of endometriosis.   
     
     
         11 . The method of  claim 1 , wherein protein is detected. 
     
     
         12 . The method of  claim 1 , wherein RNA expression is detected. 
     
     
         13 . The method of  claim 1 , wherein the sample comprises endometrial tissue. 
     
     
         14 . 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 Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3B (APOBEC3B), DEAD (Asp-Glu-Ala-Asp) box polypeptide (DEAD/H), Fibrillin 1 (FBN1), Major histocompatibility complex, class II, DOB (HLA-DOB), Lactotransferrin (LTF), Orosomucoid 2 (ORM2), Phospholipase C, beta 4 (PLCB4), POM (POM121 homolog, rat) and ZP3 fusion (POMZP3), Phosphatidic acid phosphatase, type 2B (PPAP2B), and Solute carrier family 15, member 2 (SLC15A2), and detecting altered expression of the protein as compared to a control, thereby identifying the compound. 
     
     
         15 . A kit for diagnosing endometriosis, comprising a probe for one or more nucleic acid biomarkers selected from the group consisting of Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3B (APOBEC3B), DEAD (Asp-Glu-Ala-Asp) box polypeptide (DEAD/H), Fibrillin 1 (FBN1), Major histocompatibility complex, class II, DOB (HLA-DOB), Lactotransferrin (LTF), Orosomucoid 2 (ORM2), Phospholipase C, beta 4 (PLCB4), POM (POM121 homolog, rat) and ZP3 fusion (POMZP3), Phosphatidic acid phosphatase, type 2B (PPAP2B), and Solute carrier family 15, member 2 (SLC15A2). 
     
     
         16 . The method of  claim 1 , wherein the altered expression is selected from the over expression of Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3B (APOBEC3B), over expression of Fibrillin 1 (FBN1), under expression of Phospholipase C, beta 4 (PLCB4), and under expression of Phosphatidic acid phosphatase, type 2B (PPAP2B) gene or protein, and the sample comprises early secretory phase endometrial cells or tissue. 
     
     
         17 . The method of  claim 1 , wherein the altered expression is selected from the under expression of Major histocompatibility complex, class II, DOB (HLA-DOB), under expression of POM (POM121 homolog, rat) and ZP3 fusion (POMZP3), and under expression of Solute carrier family 15, member 2 (SLC15A2) gene or protein, and the sample comprises mid secretory phase endometrial cells or tissue. 
     
     
         18 . The method of  claim 1 , wherein the altered expression is selected from under expression of DEAD (Asp-Glu-Ala-Asp) box polypeptide (DEAD/H), over expression of Lactotransferrin (LTF), and under expression of Orosomucoid 2 (ORM2) gene or protein, and the sample comprises proliferative phase endometrial cells or tissue. 
     
     
         19 . The method of  claim 1 , wherein the altered expression is the over expression of Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3B (APOBEC3B) gene or protein and the sample comprises early secretory phase endometrial cells or tissue. 
     
     
         20 . The method of  claim 1 , wherein the altered expression is the over expression of Fibrillin 1 (FBN1) gene or protein and the sample comprises early secretory phase endometrial cells or tissue. 
     
     
         21 . The method of  claim 1 , wherein the altered expression is under expression of Phospholipase C, beta 4 (PLCB4) gene or protein and the sample comprises early secretory phase endometrial cells or tissue. 
     
     
         22 . The method of  claim 1 , wherein the altered expression is under expression of Phosphatidic acid phosphatase, type 2B (PPAP2B) gene or protein and the sample comprises early secretory phase endometrial cells or tissue. 
     
     
         23 . The method of  claim 1 , wherein the altered expression is under expression of Major histocompatibility complex, class II, DOB (HLA-DOB) gene or protein and the sample comprises mid secretory phase endometrial cells or tissue. 
     
     
         24 . The method of  claim 1 , wherein the altered expression is under expression of POM (POM121 homolog, rat) and ZP3 fusion (POMZP3) gene or protein and the sample comprises mid secretory phase endometrial cells or tissue. 
     
     
         25 . The method of  claim 1 , wherein the altered expression is under expression of Solute carrier family 15, member 2 (SLC15A2) gene or protein and the sample comprises mid secretory phase endometrial cells or tissue. 
     
     
         26 . A method of diagnosing or providing a prognosis of endometriosis, the method comprising the step of:
 (i) detecting, in a biological sample from a human subject suspected of or having endometriosis, altered expression (over or under expression) of a gene or protein wherein said altered expression is selected from the group consisting of:   over expression of Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3B (APOBEC3B);   under expression of DEAD (Asp-Glu-Ala-Asp) box polypeptide (DEAD/H);   over expression of Fibrillin 1 (FBN1);   under expression of Major histocompatibility complex, class II, DOB (HLA-DOB);   over expression of Lactotransferrin (LTF);   under expression of Orosomucoid 2 (ORM2);   under expression of Phospholipase C, beta 4 (PLCB4);   under expression of POM (POM121 homolog, rat) and ZP3 fusion (POMZP3);   under expression of Phosphatidic acid phosphatase, type 2B (PPAP2B); and   under expression of Solute carrier family 15, member 2 (SLC15A2);   wherein over or under expression of at least 50% compared to a baseline value representative of expression in a human subject without endometriosis provides a diagnosis or prognosis for endometriosis; and   (ii) providing the diagnosis or the prognosis of endometriosis.   
     
     
         27 . The method of  claim 26 , wherein the biological sample comprises endometrial tissue. 
     
     
         28 . A method of treating endometriosis in a subject suffering from endometriosis, the method comprising providing a diagnosis or prognosis of endometriosis as in the method of  claim 1 , and
 treating the endometriosis accordingly.   
     
     
         29 . The method of  claim 28 , wherein the treating comprises pain killers, hormonal treatments, chemotherapy, or surgical treatments. 
     
     
         30 . A method of treating endometriosis in a subject suffering from endometriosis, the method comprising providing a diagnosis or prognosis of endometriosis as in the method of  claim 26 , and
 treating the endometriosis accordingly.   
     
     
         31 . The method of  claim 30 , wherein the treating comprises pain killers, hormonal treatments, chemotherapy, or surgical treatments.