Plasma MicroRNAs as Novel Biomarkers for Endometriosis and Endometriosis-Associated Ovarian Cancer
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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 patients with endometriosis and ovarian cancer from healthy individuals. Experimental Design: 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. 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. Clin Cancer Res; 19(5); 1213–24. ©2013 AACR.
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Reduced plasma levels of miR-17-5p, miR-20a, and miR-22 and elevated plasma levels of miR-16, miR-191, and miR-195 have been found in women with endometriosis compared with women without endometriosis.
“Reduced plasma levels of miR-17-5p, miR-20a, and miR-22 [86] and elevated plasma levels of miR-16, miR-191, and miR-195 [87] have been found in women with endometriosis compared with women without endometriosis.”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [87]
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1 retracted
RETRACTED: MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer
Taylor, D. D., & Gerçel-Taylor, Ç. (2008) · Gynecologic Oncology · doi:10.1016/j.ygyno.2008.04.033 · Cited by 2,289 · see citing works
RetractedControlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
Analyzing real-time PCR data by the comparative CT method
Schmittgen, T. D., & Livak, K. J. (2008) · Nature Protocols · doi:10.1038/nprot.2008.73 · Cited by 26,190 · see citing works
Siegel, R., Naishadham, D., & Jemal, A. (2012) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20138 · Cited by 10,679 · see citing works
MicroRNA expression profiles classify human cancers
Lü, J., Getz, G. A., Miska, E. A., Alvarez-Saavedra, E., Lamb, J., Peck, D., Sweet-Cordero, A., Ebert, B. L., Mak, R. H., Ferrando, A. A., et al. (2005) · Nature · doi:10.1038/nature03702 · Cited by 9,497 · see citing works
Circulating microRNAs as stable blood-based markers for cancer detection
Mitchell, P. S., Parkin, R. K., Kroh, E. M., Fritz, B. R., Wyman, S. K., Pogosova-Agadjanyan, E. L., Peterson, A., Noteboom, J., O'Briant, K. C., Allen, A., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804549105 · Cited by 7,969 · see citing works
Discriminant Analysis and Statistical Pattern Recognition.
Hawkins, D. M., & McLachlan, G. J. (1993) · Journal of the American Statistical Association · doi:10.2307/2290355 · Cited by 2,662 · see citing works
Direct multiplexed measurement of gene expression with color-coded probe pairs
Geiss, G. K., Bumgarner, R. E., Birditt, B., Dahl, T., Dowidar, N., Dunaway, D. L., Fell, H. P., Ferree, S., George, R. D., Grogan, T., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1385 · Cited by 2,066 · see citing works
Giudice, L. C. (2010) · New England Journal of Medicine · doi:10.1056/nejmcp1000274 · Cited by 1,924 · see citing works
Garzon, R., Calin, G. A., & Croce, C. M. (2009) · Annual Review of Medicine · doi:10.1146/annurev.med.59.053006.104707 · Cited by 1,791 · see citing works
Control of translation and mRNA degradation by miRNAs and siRNAs: Table 1.
Valencia-Sanchez, M. A., Liu, J., Hannon, G. J., & Parker, R. (2006) · Genes & Development · doi:10.1101/gad.1399806 · Cited by 1,751 · see citing works
<i>ARID1A</i> Mutations in Endometriosis-Associated Ovarian Carcinomas
Wiegand, K. C., Shah, S. P., Al-Agha, O. M., Zhao, Y., Tse, K., Zeng, T., Senz, J., McConechy, M. K., Anglesio, M. S., Kalloger, S. E., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1008433 · Cited by 1,712 · see citing works
MicroRNA Signatures in Human Ovarian Cancer
Iorio, M. V., Visone, R., Leva, G. D., Donati, V. L., Petrocca, F., Casalini, P., Taccioli, C., Volinia, S., Liu, C.-G., Alder, H., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1936 · Cited by 1,396 · see citing works
Serum MicroRNAs Are Promising Novel Biomarkers
Gilad, S., Meiri, E., Yogev, Y., Benjamin, S., Lebanony, D., Yerushalmi, N., Benjamin, H., Kushnir, M., Cholakh, H., Melamed, N., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003148 · Cited by 1,349 · see citing works
Discriminant Analysis and Statistical Pattern Recognition
McLachlan, G. J. (1992) · Wiley series in probability and statistics · doi:10.1002/0471725293 · Cited by 1,272 · see citing works
miR‐21: a small multi‐faceted RNA
Krichevsky, A. M., & Gabriely, G. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00556.x · Cited by 987 · see citing works
Cannistra, S. (1993) · New England Journal of Medicine · doi:10.1056/nejmra041842 · Cited by 957 · see citing works
Pearce, C. L., Templeman, C., Rossing, M. A., Lee, A., Near, A. M., Webb, P. M., Nagle, C. M., Doherty, J. A., Cushing-Haugen, K. L., Wicklund, K. G., et al. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70404-1 · Cited by 939 · see citing works
MicroRNAs and Cancer: Short RNAs Go a Long Way
Ventura, A., & Jacks, T. (2009) · Cell · doi:10.1016/j.cell.2009.02.005 · Cited by 893 · see citing works
Ovarian Carcinoma Subtypes Are Different Diseases: Implications for Biomarker Studies
Köbel, M., Kalloger, S. E., Boyd, N., McKinney, S., Mehl, E., Palmer, C., Leung, S., Bowen, N. J., Ionescu, D. N., Rajput, A., et al. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050232 · Cited by 814 · see citing works
Hu, Z., Chen, X., Zhao, Y., Tian, T., Jin, G., Shu, Y., Chen, Y., Xu, L., Zen, K., Zhang, C., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.24.9342 · Cited by 649 · see citing works
Resnick, K. E., Alder, H., Hagan, J. P., Richardson, D. L., Croce, C. M., & Cohn, D. E. (2008) · Gynecologic Oncology · doi:10.1016/j.ygyno.2008.08.036 · Cited by 647 · see citing works
Dinulescu, D. M., Ince, T. A., Quade, B. J., Shafer, S. A., Crowley, D. G., & Jacks, T. (2004) · Nature Medicine · doi:10.1038/nm1173 · Cited by 601 · see citing works
Wang, J., Chen, J., Chang, P., Leblanc, A. B., Li, D., Abbruzzesse, J. L., Frazier, M. L., Killary, A. M., & Sen, S. (2009) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-09-0094 · Cited by 560 · see citing works
深井順也, & 西尾, 和. (2006) · Mebio oncology · Cited by 557 · see citing works
Extracellular miRNAs: the mystery of their origin and function
Turchinovich, A. A., Weiz, L., & Burwinkel, B. (2012) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2012.08.003 · Cited by 520 · see citing works
New tumor markers: CA125 and beyond
Bast, R. C., Badgwell, D. B., Lü, Z., Marquez, R. T., Rosen, D. G., LIU, J., Baggerly, K., Atkinson, E. N., Skates, S. J., Zhang, Z., et al. (2005) · International Journal of Gynecological Cancer · doi:10.1111/j.1525-1438.2005.00441.x · Cited by 502 · see citing works
Clarke‐Pearson, D. L. (2009) · New England Journal of Medicine · doi:10.1056/nejmcp0901926 · Cited by 401 · see citing works
<b>Ovarian atypical endometriosis: its close association with malignant epithelial tumours</b>
FUKUNAGA, M., NOMURA, K., ISHIKAWA, E., & USHIGOME, S. (1997) · Histopathology · doi:10.1046/j.1365-2559.1997.d01-592.x · Cited by 333 · cited 1× · see citing works
“of the atypical ovarian endometriosis with ovarian cancer (20), suggesting a transition spectrum of nonatypical to atypical and malignant variants (21).”
The role of CA125 in clinical practice
Moss, E. L., Hollingworth, J., & Reynolds, T. (2005) · Journal of Clinical Pathology · doi:10.1136/jcp.2004.018077 · Cited by 309 · see citing works
Cramer, D. W., Bast, R. C., Berg, C. D., Diamandis, E. P., Godwin, A. K., Hartge, P. A., Lokshin, A. E., Lu, K. H., McIntosh, M. W., Mor, G., et al. (2011) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-10-0195 · Cited by 300 · see citing works
Circulating Micro-RNAs as Potential Blood-Based Markers for Early Stage Breast Cancer Detection
Schrauder, M. G., Strick, R., Schulz‐Wendtland, R., Strissel, P. L., Kahmann, L., Loehberg, C. R., Lux, M. P., Jud, S. M., Hartmann, A., Hein, A., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029770 · Cited by 250 · see citing works
Liu, X., Zhu, W., Huang, Y., Ma, L., Zhou, S., Wang, Y., Fang, Z., Zhou, J., & Zhang, Y. (2011) · Medical Oncology · doi:10.1007/s12032-011-9923-y · Cited by 246 · see citing works
The relationship of endometriosis and ovarian malignancy: a review
Nezhat, F. R., Datta, M., Hanson, V., Pejovic, T. B., Nezhat, C., & NEZHAT, C. R. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2008.08.007 · Cited by 246 · see citing works
Li, B., Zhao, Y., Guo, G., Li, W., Zhu, E., Luo, X. L., Mao, X., Zou, Q., Yu, P.-W., Zuo, Q., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041629 · Cited by 242 · see citing works
Wyman, S. K., Parkin, R. K., Mitchell, P. S., Fritz, B. R., O'Briant, K. C., Godwin, A. K., Urban, N. D., Drescher, C. W., Knudsen, B. S., & Tewari, M. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005311 · Cited by 233 · see citing works
Endometriosis and ovarian cancer: Thoughts on shared pathophysiology
Ness, R. B. (2003) · American Journal of Obstetrics and Gynecology · doi:10.1067/mob.2003.408 · Cited by 227 · see citing works
Endometriosis and the neoplastic process
Varma, R., Rollason, T. P., Gupta, J. K., & Maher, E. R. (2004) · Reproduction · doi:10.1530/rep.1.00020 · Cited by 216 · see citing works
Endometriosis and Ovarian Cancer
Wei, J., William, J., & Bulun, S. E. (2011) · International Journal of Gynecological Pathology · doi:10.1097/pgp.0b013e31821f4b85 · Cited by 174 · see citing works
Malignant Transformation of Ovarian Endometriosis
Nishida, M., Watanabe, K., Sato, N., & Ichikawa, Y. (2000) · Gynecologic and Obstetric Investigation · doi:10.1159/000052874 · Cited by 165 · see citing works
Cluster analysis and related techniques in medical research
McLachlan, G. J. (1992) · Statistical Methods in Medical Research · doi:10.1177/096228029200100103 · Cited by 157 · see citing works
Anti-angiogenic treatment strategies for the therapy of endometriosis
Laschke, M. W., & Menger, M. D. (2012) · Human Reproduction Update · doi:10.1093/humupd/dms026 · Cited by 151 · see citing works
Engel, J., Eckel, R., Schubert-Fritschle, G., et al. (2002) · European Journal of Cancer · doi:10.1016/s0959-8049(02)00495-1 · Cited by 145 · see citing works
Prognostic Importance of Hyperplasia and Atypia in Endometriosis
Seidman, J. D. (1996) · International Journal of Gynecological Pathology · doi:10.1097/00004347-199601000-00001 · Cited by 126 · see citing works
MicroRNAs in ovarian carcinomas
Dahiya, N., & Morin, P. J. (2009) · Endocrine Related Cancer · doi:10.1677/erc-09-0203 · Cited by 109 · see citing works
Kandalaft, L. E., Motz, G. T., Busch, J. I., & Coukos, G. (2010) · Current topics in microbiology and immunology · doi:10.1007/82_2010_95 · Cited by 96 · see citing works
Prevalence of endometriosis in malignant epithelial ovary tumours
Oral, E., İlvan, Ş., Tustas, E., Körbeyli, B., Beşe, T., Demirkıran, F., Arvas, M., & Kösebay, D. (2003) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/s0301-2115(03)00047-2 · Cited by 93 · see citing works
Budiu, R. A., Diaconu, I., Chrissluis, R., Dricu, A., Edwards, R. P., & Vlad, A. (2009) · Disease Models & Mechanisms · doi:10.1242/dmm.002535 · Cited by 52 · see citing works
Self-citationDiscovery and application of protein biomarkers for ovarian cancer
Gagnon, A., & Ye, B. (2008) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0b013e3282f226a5 · Cited by 46 · see citing works
Gail, M. H., Fears, T. R., Hoover, R. N., et al. (1996) · PubMed · Cited by 38 · see citing works
Endometriosis: an invasive disease
Garry, R. (2001) · Gynaecological Endoscopy · doi:10.1046/j.1365-2508.2001.00428.x · Cited by 34 · see citing works
Frequency of ovarian endometriosis in epithelial ovarian cancer patients.
Dzatic-Smiljkovic, O., Vasiljević, M., Djukic, M., et al. (2011) · PubMed · Cited by 28 · see citing works
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Cited by
Sorted by citations
Update on biomarkers for the detection of endometriosis
Fassbender, A., Burney, R. O., F. O, D., D’Hooghe, T., & Giudice, L. (2015) · BioMed Research International · doi:10.1155/2015/130854 · Cited by 195 · see citing works
Circulating microRNAs as potential biomarkers for endometriosis
Cho, S., Mutlu, L., Grechukhina, O., & Taylor, H. S. (2015) · Fertility and Sterility · doi:10.1016/j.fertnstert.2015.02.013 · Cited by 181 · see citing works
Fassbender, A., Vodolazkaia, A., Saunders, P., Lebovic, D., Waelkens, E., De Moor, B., & D'Hooghe, T. (2013) · Fertility and Sterility · doi:10.1016/j.fertnstert.2013.01.097 · Cited by 150 · see citing works
Systems genetics view of endometriosis: a common complex disorder
Baranov, V. S., Ivaschenko, T. E., Liehr, T., & Yarmolinskaya, M. I. (2015) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2014.11.036 · Cited by 62 · see citing works
Endometriosis, infertility and MicroRNA’s: A review
Raja, M. H. R., Farooqui, N., Zuberi, N., Ashraf, M., Azhar, A., Baig, R., Badar, B., & Rehman, R. (2021) · Journal of Gynecology Obstetrics and Human Reproduction · doi:10.1016/j.jogoh.2021.102157 · Cited by 53 · see citing works
Noninvasive biomarkers of endometriosis: myth or reality?
Lanišnik Rižner, T. (2014) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.2014.899905 · Cited by 52 · see citing works
The Endometriotic Tumor Microenvironment in Ovarian Cancer
Wendel, J. R. H., Wang, X., & Hawkins, S. M. (2018) · Cancers · doi:10.3390/cancers10080261 · Cited by 51 · see citing works
Zafari, N., Tarafdari, A. M., Izadi, P., Noruzinia, M., Yekaninejad, M. S., Bahramy, A., & Mohebalian, A. (2021) · Reproductive Sciences · doi:10.1007/s43032-020-00415-z · Cited by 36 · see citing works
Monnaka, V. U., Hernandes, C., Heller, D., & Podgaec, S. (2021) · Einstein (São Paulo) · doi:10.31744/einstein_journal/2021rw5704 · Cited by 33 · see citing works
Endometriosis and ovarian cancer
Králíčková, M. (2014) · World Journal of Clinical Oncology · doi:10.5306/wjco.v5.i5.800 · Cited by 27 · see citing works
- Authors
- Suryawanshi, S., Vlad, A. M., Lin, H.-M., Mantia-Smaldone, G., Laskey, R., Lee, M., Lin, Y., Donnellan, N., Klein-Patel, M., Lee, T., Mansuria, S., Elishaev, E., Budiu, R., Edwards, R. P., & Huang, X.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Huang, Xin
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2013-03-01
- Volume
- 19
- Issue
- 5
- Pages
- 1213-1224
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC3596045
- OpenAlex
- W2153569033
- Cited by
- 197
- References
- 52
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 10 · 2023: 8 · 2022: 8 · 2021: 18 · 2020: 18 · 2019: 13 · 2018: 18 · 2017: 17 · 2016: 20 · 2015: 30 · 2014: 16 · 2013: 7
- FWCI
- 29.38
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Magee-Womens Research Institute
- National Institutes of Health (UL1TR000005)
- National Cancer Institute (NIH/NCI 1 R01 CA163462-01, R01CA163462, P30CA047904)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Keywords
- endometriosis, endometriosis-associated ovarian cancer, plasma microRNA, diagnostic biomarkers, microRNA signature, serous ovarian cancer, double transgenic mouse model, differentially expressed miRNAs, disease discrimination
- MeSH terms
- Adult, Aged, Animals, Endometriosis, Endometrium, Female, Follow-Up Studies, Humans, Middle Aged, Neoplasm Staging, Ovarian Neoplasms, Prognosis, Retrospective Studies, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Survival Rate, Case-Control Studies, Proto-Oncogene Proteins p21(ras), Adenocarcinoma, Clear Cell, Cystadenocarcinoma, Serous, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, MicroRNAs, PTEN Phosphohydrolase, Mice
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