Biological markers in the diagnosis of endometriosis
Combinations of the novel biological markers that can be used in the diagnosis of endometriosis are provided. The objective of the invention is to detect biological markers that are expressed differently in eMSCs isolated from endometrial biopsy samples in the diagnosis of endometriosis compared to healthy eMSCs. A tissue transglutaminase is configured as a biomarker for a diagnosis of an endometriosis in isolated endometrial mesenchymal stem cells derived from an endometrial biopsy and/or a menstrual blood from endometriosis patients.
1 . A diagnostic kit for detecting endometriosis in a human subject, comprising:
(a) at least one reagent for detecting tissue transglutaminase (tTG) mRNA expression, tTG protein expression, or both; and
(b) at least one reagent for detecting at least one biomarker selected from the group consisting of cluster of differentiation 146 (CD146), sushi domain containing protein 2 (SUSD2), integrin beta 1 (ITGB1), and platelet derived growth factor receptor (PDGFR);
wherein the diagnostic kit is configured to measure an expression level of the tTG and the at least one biomarker in mesenchymal stem cells isolated from eutopic endometrial tissue and/or menstrual blood.
2 . The diagnostic kit of claim 1 , wherein an expression level of the tTG and the at least one biomarker, each relative to its corresponding reference level, is indicative of endometriosis.
3 . The diagnostic kit of claim 1 , wherein the reagent for detecting tTG comprises an antibody.
4 . The diagnostic kit of claim 1 , wherein the reagent for detecting tTG comprises at least one nucleic acid probe or primer.
5 . The diagnostic kit of claim 1 , wherein the kit is configured for multiplex detection.
6 . A method of evaluating a response to treatment in a human subject having endometriosis, comprising:
(a) isolating mesenchymal stem cells from eutopic endometrial tissue and/or menstrual blood obtained from the subject at a first time point before a drug treatment and at a second time point after the drug treatment;
(b) quantifying tissue transglutaminase (tTG) mRNA and/or protein expression and expression of at least one biomarker selected from CD146, SUSD2, ITGB1, and PDGFR in the isolated mesenchymal stem cells;
(c) comparing expression levels between the first and second time points; and
(d) determining a response to treatment based on a change in expression levels, wherein the quantification is optionally performed using the diagnostic kit of claim 1 .
7 . The method of claim 6 , wherein the expression level of the tTG mRNA is at least 2.5-fold higher than the reference level.
8 . The method of claim 6 , wherein the expression level of the tTG protein is at least 4-fold higher than the reference level.
9 . The method of claim 6 , wherein the expression level of the tTG and the at least one biomarker are each increased relative to the corresponding reference levels, and wherein the combined increase is indicative of endometriosis.
10 . The method of claim 6 , wherein a reduction of the expression level of the tTG results in a corresponding decrease in the expression of the at least one biomarker.