Plasma microRNAs as novel biomarkers for endometriosis and endometriosis-associated ovarian cancer.
OBJECTIVE
Endometriosis, a largely benign, chronic inflammatory disease, is an independent risk factor for endometrioid and clear cell epithelial ovarian tumors. We aimed to identify plasma miRNAs that can be used to differentiate patients with endometriosis and ovarian cancer from healthy individuals.


METHODS
We conducted a two-stage exploratory study to investigate the use of plasma miRNA profiling to differentiate between patients with endometriosis, patients with endometriosis-associated ovarian cancer (EAOC), and healthy individuals. In the first stage, using global profiling of more than 1,000 miRNAs via reverse transcriptase quantitative PCR (RT-qPCR) in a 20-patient initial screening cohort, we identified 23 candidate miRNAs, which are differentially expressed between healthy controls (n = 6), patients with endometriosis (n = 7), and patients with EAOC (n = 7) based on the fold changes. In the second stage, the 23 miRNAs were further tested in an expanded cohort (n = 88) of healthy individuals (n = 20), endometriosis (n = 33), EAOC (n = 14), and serous ovarian cancer cases (SOC; n = 21, included as controls).


RESULTS
We identified three distinct miRNA signatures with reliable differential expression between healthy individuals, patients with endometriosis, and patients with EAOC. When profiled against the control SOC category, our results revealed different miRNAs, suggesting that the identified signatures are reflective of disease-specific pathogenic mechanisms. This was further supported by the fact that the majority of miRNAs differentially expressed in human EAOCs were mirrored in a double transgenic mouse EAOC model.


CONCLUSIONS
Our study reports for the first time that distinct plasma miRNA expression patterns may serve as highly specific and sensitive diagnostic biomarkers to discriminate between healthy, endometriosis, and EAOC cases.
Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Swati
S
Suryawanshi
Anda M
AM
Vlad
Hui-Min
HM
Lin
Gina
G
Mantia-Smaldone
Robin
R
Laskey
Minjae
M
Lee
Yan
Y
Lin
Nicole
N
Donnellan
Marcia
M
Klein-Patel
Ted
T
Lee
Suketu
S
Mansuria
Esther
E
Elishaev
Raluca
R
Budiu
Robert P
RP
Edwards
Xin
X
Huang
D018262:Adenocarcinoma, Clear Cell / Q000097:blood / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D018284:Cystadenocarcinoma, Serous / Q000097:blood / Q000235:genetics / Q000473:pathology; D004715:Endometriosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000502:physiology; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
D014408:Biomarkers, Tumor; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)