Plasma MicroRNAs as Novel Biomarkers for Endometriosis and Endometriosis-Associated Ovarian Cancer

Abstract

Purpose 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 endometriosis and ovarian cancer patients from healthy individuals. Experimental design We conducted a two-stage exploratory study to investigate the utility of plasma miRNA profiling to differentiate between endometriosis, 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), endometriosis (n=7), and EAOC (n=7) patients 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, endometriosis, and EAOC patients. 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 EAOC were mirrored in a double transgenic mouse EAOC model. Conclusion 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.

Comparative systems genetics view of endometriosis and uterine leiomyoma: Two sides of the same coin?

“…Given the diverse roles that miRNAs play in cellular functions it is not surprising that they play key regulatory roles in the pathogenesisis of EM. Numerous miRNAs are mis-expressed in EM cells and abnormal profiles of miRNAs are reported [Suryawanshi et al 2013]. Some of these miRNA are definitely over-or under-expressed in EM tissues.…”

Endometriosis-Search for Biomarkers

“…These microRNAs were subsequently further evaluated in a larger cohort. The results showed that plasma microRNA expressing patterns might serve as specific and reliable diagnostic biomarkers (Suryawanshi et al, 2013) resulting in some authors suggesting than microRNA studies will lead to changes in current treatment of both endometriosis and ovarian cancer (Neto et al, 2014).…”

Carcinogenic activity of PbS quantum dots screened using exosomal biomarkers secreted from HEK293 cells

“…31,32 The criteria for biomarker selection were 1) dose dependent increase or decrease following PbS-MPA treatment at 5 µg/mL and 50 µg/mL, 2) a change in expression of at least more than threefold following treatment with 50 µg/mL PbS-MPA QDs (in comparison with the untreated control sample), and 3) a statistically significant change in expression level in comparison with that of control sample (P,0.05). Five miRNAs, hsa-miR-525-5p, hsa-miR-527, hsa-miR-532-3p, hsa-miR-548e, and hsa-miR-199a-5p, met the criteria and were proposed as exosomal biomarkers of exposure of HEK293 cells to PbS-MPA.…”