Circulating microRNA as biomarkers for endometriosis

1. A noninvasive method of detecting miRNA in a subject, the method comprising:

(a) providing a biological sample comprising saliva from the subject, wherein the subject has endometriosis or is suspected of having endometriosis, and wherein the biological sample comprises at least one miRNA that is a biomarker for endometriosis, wherein at least one miRNA that is a biomarker for endometriosis comprises let-7b miRNA; and

(b) performing an in vitro amplification procedure on the at least one miRNA that is a biomarker for endometriosis; and

(c) detecting a level of the at least one miRNA that is a biomarker for endometriosis in the biological sample comprising saliva from the subject; and

(d) treating the subject for endometriosis based on the detected level of the at least one miRNA that is a biomarker for endometriosis in the biological sample comprising saliva from the subject, wherein the treating the subject comprises administering a hormonal treatment, an oral contraceptive, a progestin, a GnRH agonist, an androgen, an aromatase inhibitor, a non-steroidal anti-inflammatory drug, or a combination thereof, wherein the detected level of the let-7b miRNA is downregulated, and wherein the downregulation is statistically significant.

2. The method of claim 1 , wherein the method further comprises detecting at least one miRNA selected from the group consisting of let-7a, let-7c, let-7d, let-7e, let-7f, mir135a, and mir135b.

3. The method of claim 1 , wherein the method further comprises detecting at least one miRNA selected from the group consisting of let-7d and let-7f.

4. The method of claim 1 , wherein the subject is human.

5. The method of claim 1 , wherein the in vitro amplification procedure comprises at least one technique selected from the group consisting of reverse transcription, PCR, sequencing and a microarray.

6. The method of claim 1 wherein the treating the subject comprises administering an oral contraceptive to the subject.

7. The method of claim 1 , wherein the treating the subject comprises administering a progestin to the subject.

8. The method of claim 1 , wherein the treating the subject comprises administering to the subject a GnRH agonist, an androgen, an aromatase inhibitor, a non-steroidal anti-inflammatory drug, or combination thereof.

9. The method of claim 1 , wherein the detected level of the at least one miRNA that is a biomarker for endometriosis is a statistically significant indication of endometriosis.

10. The method of claim 1 , wherein the biological sample is acellular.

11. The method of claim 1 , wherein the method is at least 90% sensitive for detecting endometriosis.

12. The method of claim 1 , wherein the method is at least 90% specific for detecting endometriosis.

13. The method of claim 1 , wherein the method is at least 90% accurate for detecting endometriosis.

14. The method of claim 1 , wherein a source of the at least one miRNA is an exosome.

15. The method of claim 1 , wherein the at least one miRNA is detected at multiple time points.

16. The method of claim 1 , further comprising diagnosing or providing a prognosis for endometriosis in a subject, based on the detected level of the at least one miRNA that is a biomarker for endometriosis.

17. The method of claim 16 , wherein the diagnosing comprises diagnosing endometriosis during a proliferative phase of endometriosis in the subject.

18. The method of claim 1 , wherein treating the subject comprises administering a hormonal treatment to the subject.

19. The method of claim 1 , wherein the method is at least 80% sensitive for detecting endometriosis.

20. The method of claim 1 , wherein the method is at least 80% specific for detecting endometriosis.

21. The method of claim 1 , wherein the sample is a saliva sample and further comprising extracting RNA comprising the at least one miRNA that is a biomarker for endometriosis from the saliva sample prior to (b).

22. The method of claim 1 , wherein the treating the subject for endometriosis based on the detected level of the at least one miRNA that is a biomarker for endometriosis in the saliva sample comprises administering a progestin to the subject.

23. The method of claim 1 , wherein the treating the subject for endometriosis based on the detected level of the at least one miRNA that is a biomarker for endometriosis in the saliva sample comprises administering a GnRH agonist to the subject.

24. The method of claim 1 , wherein the in vitro amplification procedure comprises a sequencing assay.

25. The method of claim 24 , wherein the sequencing assay is a next generation sequencing assay.

26. A noninvasive method of detecting endometriosis in a subject, the method comprising detecting in a biological sample obtained from a body fluid altered expression of at least one miRNA selected from the group consisting of let-7a, let-7b, and let-7d, in a subject suspected of or having endometriosis; and treating the subject for endometriosis based on the detected level of the at least one miRNA in the subject, wherein the treating the subject comprises administering a hormonal treatment, an oral contraceptive, a progestin, a GnRH agonist, an androgen, an aromatase inhibitor, a non-steroidal anti-inflammatory drug, or a combination thereof, wherein the detected level of let-7a, let-7b, or let-7d is downregulated, and wherein the downregulation is statistically significant.

27. The method of claim 26 , wherein the at least one gene comprises let-7b.

28. The method of claim 26 , wherein the biological sample is at least one biological sample selected from the group consisting of blood, serum, plasma, saliva, and urine.

29. The method of claim 26 , wherein treating the subject comprises administering a hormonal treatment to the subject.

30. The method of claim 26 , wherein the at least one miRNA comprises let-7b.

31. The method of claim 26 , wherein the biological sample is selected from the group consisting of blood, serum, and plasma.

32. The method of claim 26 , wherein the biological sample is serum.

33. The method of claim 26 , wherein the biological sample is plasma.

34. The method of claim 26 , wherein the method is at least 80% sensitive for detecting endometriosis.

35. The method of claim 26 , wherein the method is at least 80% specific for detecting endometriosis.

36. The method of claim 32 , wherein the at least one miRNA comprises let-7a or let-7b.

37. The method of claim 33 , wherein the at least one miRNA comprises let-7a or let-7b.

38. The method of claim 36 , further comprising extracting RNA comprising the at least one miRNA from the serum sample.

39. The method of claim 37 , further comprising extracting RNA comprising the at least one miRNA from the plasma sample.

40. The method of claim 32 , wherein the at least one miRNA comprises let-7b.

41. The method of claim 33 , wherein the at least one miRNA comprises let-7b.

42. The method of claim 40 , wherein the detected level of the let-7b is downregulated.

43. The method of claim 41 , wherein the detected level of the let-7b is downregulated.

44. The method of claim 38 , wherein the treating the subject for endometriosis based on the detected level of the at least one miRNA that is a biomarker for endometriosis in the saliva sample comprises administering a progestin to the subject.

45. The method of claim 39 , wherein the treating the subject for endometriosis based on the detected level of the at least one miRNA that is a biomarker for endometriosis in the saliva sample comprises administering a progestin to the subject.

46. The method of claim 38 , wherein the treating the subject for endometriosis based on the detected level of the at least one miRNA that is a biomarker for endometriosis in the saliva sample comprises administering a GnRH agonist to the subject.

47. The method of claim 39 , wherein the treating the subject for endometriosis based on the detected level of the at least one miRNA that is a biomarker for endometriosis in the saliva sample comprises administering a GnRH agonist to the subject.

48. The method of claim 38 , wherein the detecting comprises a sequencing assay.

49. The method of claim 48 , wherein the sequencing assay is a next generation sequencing assay.

50. The method of claim 39 , wherein the detecting comprises a sequencing assay.

51. The method of claim 50 , wherein the sequencing assay is a next generation sequencing assay.