Methods of diagnosing endometriosis
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.
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:
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).
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 Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3B (APOBEC3B), Fibrillin 1 (FBN1), Phospholipase C, beta 4 (PLCB4), or Phosphatidic acid phosphatase, type 2B (PPAP2B), 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 Major histocompatibility complex, class II, DOB (HLA-DOB), POM (POM121 homolog, rat) and ZP3 fusion (POMZP3), and Solute carrier family 15, member 2 (SLC15A2), and the sample comprises mid secretory phase endometrial cells or tissue.
7. The method of claim 1 , wherein the gene or protein is selected from DEAD (Asp-Glu-Ala-Asp) box polypeptide (DEAD/H), Lactotransferrin (LTF), and Orosomucoid 2 (ORM2), 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:
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).
9. The method of claim 8 , 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.
10. The method of claim 8 , 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.
11. The method of claim 8 , 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.
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.