PLASMA MICRORIBONUCLEIC ACIDS AS BIOMARKERS FOR ENDOMETRIOSIS AND ENDOMETRIOSIS-ASSOCIATED OVARIAN CANCER
The present invention relates to methods and compositions for differentiating between absence of disease, endometriosis, and EAOC or serous ovarian cancer in a subject. It is based, at least in part, on the discovery that certain microRNAs are associated with each of these conditions.
1 . A kit for diagnosing endometriosis, endometriosis-associated ovarian cancer, or serous ovarian cancer, comprising measuring means for one or more of mir 15b, mir 16, mir 21, mir 191, mir 195, mir 362-5p, mir 376a, mir 628-3p, mir 744, mir 766, mir 1246, mir 1274a, mir 1308, mir 1915, mir 1973, mir 1974, mir 1975, mir 1977, mir 1978, mir 1979, mir 4284 where the measuring means is either (i) for each biomarker to be measured, a pair of oligonucleotide primers that may be used to amplify the biomarker or (ii) a microarray where said biomarker(s) constitute at least 10 percent of the species of biomarkers represented on the microarray.
2 . The kit according to claim 1 , for use in distinguishing between a healthy subject, a subject having endometriosis, a subject having endometriosis associated ovarian cancer and a subject having serous ovarian cancer, comprising measuring means for mir 16, mir 21 and mir 191 and at least one of mir 195, mir 4284, mir 362-5p, mir 1274a, mir 628-3p, mir 1915 and mir 1975 and combinations thereof.
3 . The kit according to claim 2 , further comprising a healthy control sample.
4 . The kit according to claim 2 , further comprising an endometriosis control sample.
5 . The kit according to claim 2 , further comprising an endometriosis associated ovarian control sample.
6 . The kit according to claim 2 , further comprising a serous ovarian cancer control sample.
7 . The kit according to claim 1 , for use in distinguishing between a healthy subject and a subject having endometriosis, comprising measuring means for one or more biomarker selected from the group consisting of mir 16; mir 15b; mir 191; mir 195; mir 1973; mir 1974; mir 1977, mir 1978, mir 1979, mir 4284 and mir 362-5p and combinations thereof.
8 . The kit according to claim 7 , further comprising a healthy control sample.
9 . The kit according to claim 7 , further comprising an endometriosis control sample.
10 . The kit according to claim 1 , for use in distinguishing between a healthy subject and a subject with endometriosis-associated ovarian cancer comprising measuring means for one or more biomarker selected from the group consisting of mir 16, mir 21, mir 15b, mir 191, mir 195, mir 1973, mir 1974, mir 1977, mir 1979, mir 766 and mir 4284 and combinations thereof.
11 . The kit according to claim 10 , further comprising a healthy control sample.
12 . The kit according to claim 10 , further comprising an endometriosis-associated ovarian cancer control sample.
13 . The kit according to claim 1 , for use in distinguishing between a healthy subject and a subject with serous ovarian cancer comprising measuring means for one or more biomarker selected from the group consisting of mir 4284, mir 1974, mir 16, mir 1977, mir 1975, mir 195, mir 1978, mir 21, mir 362-5p, mir 15b, mir 1308 and mir 191 and combinations thereof.
14 . The kit according to claim 13 , further comprising a healthy control sample.
15 . The kit according to claim 13 , further comprising an serous ovarian cancer control sample.
16 . The kit according to claim 1 , for use in distinguishing between a subject with endometriosis and a subject with endometriosis-associated ovarian cancer comprising measuring means for one or more biomarker selected from the group consisting of mir 362-5p, mir 1274a, mir-21, mir 766, mir 1975, mir 1308, mir 191, mir 744, mir 376a, and mir 1246 and combinations thereof.
17 . The kit according to claim 16 , further comprising an endometriosis control sample.
18 . The kit according to claim 16 , further comprising an endometriosis-associated ovarian cancer control sample.
19 . The kit according to claim 1 for use in distinguishing between a subject with endometriosis and a subject with serous ovarian cancer comprising measuring means for one or more biomarker selected from the group consisting of mir-1915, mir 362-5p, and combinations thereof.
20 . The kit according to claim 19 , further comprising an endometriosis control sample.
21 . The kit according to claim 19 , further comprising a serous ovarian cancer control sample.
22 . The kit according to claim 1 for distinguishing between endometriosis-associated ovarian cancer and serous ovarian cancer comprising measuring means for one or more biomarker selected from the group consisting of mir 21, mir 16, mir 191, mir 15b, mir 1975, mir 1246, mir 362-5p, mir 1979, mir 1973 and mir 195, and combinations thereof.
23 . The kit according to claim 22 , further comprising an endometriosis-associated ovarian cancer control sample.
24 . The kit according to claim 22 , further comprising a serous ovarian cancer.
25 . A method of diagnosing a subject, comprising (a) obtaining a plasma sample from the subject; (b) purifying nucleic acid from the sample; (c) amplifying, from the nucleic acid, one or more microRNA biomarker that distinguishes between a healthy subject and (i) a subject having endometriosis; (ii) a subject with endometriosis associated ovarian cancer; and (iii) a subject having serous ovarian cancer; (d) measuring the level(s) of the one or more microRNA amplified according to step (c); (e) comparing the level of the one or more biomarker in the plasma sample to a control level or control levels; and (f) reporting if a diagnosis of endometriosis, endometriosis associated ovarian cancer or serous ovarian cancer is indicated.
26 . A method of evaluating whether a subject having endometriosis has developed ovarian cancer, comprising (a) obtaining a plasma sample from the subject; (b) purifying nucleic acid from the sample; (c) amplifying, from the nucleic acid, one or more microRNA biomarker that distinguishes between a subject with endometriosis and (i) a subject with endometriosis associated ovarian cancer and/or (ii) a subject with serous ovarian cancer; (d) measuring the level(s) of the one or more microRNA amplified according to step (c); (e) comparing the level of the one or more biomarker in the plasma sample to a control level or control levels; and (f) reporting if a diagnosis of endometriosis associated ovarian cancer or serous ovarian cancer is indicated.