Skip to main content

Advertisement

SpringerLink
Log in

Emerging diagnostic, prognostic and therapeutic biomarkers for ovarian cancer

  • Review
  • Published:
Cellular Oncology Aims and scope Submit manuscript

Abstract

Background

In spite of various treatment options currently available, ovarian cancer (OC) still remains a leading cause of death in women world-wide. Diagnosis at an early stage is one of the most important factors that determines survival. Current clinical diagnostic tools have, however, a limited efficacy in early OC detection. Therefore, there is a critical need for new (early) diagnostic biomarkers and tools. Through advances in genomic, proteomic and metabolomic techniques, several novel molecular OC biomarkers have recently been identified. These biomarkers are currently subject to validation. In addition, integration of genomic, proteomic and metabolomic data, in conjunction with epidemiologic and clinical data, is considered essential for obtaining useful results. Interesting recent work has already shown that specific diagnostic biomarkers, such as BRCA mutations, may have profound therapeutic implications. Here, we review the current state of OC research through literature and database searches, with a focus on various recently identified biomarkers via different technologies for the (early) diagnosis, prognosis and treatment of OC.

Conclusions

Multi-biomarker panels accompanied by a meticulous determination of their sensitivity and specificity, as well their validation, using multivariate analyses will be critical for its clinical application, including early OC detection and tailor-made OC treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D.M. Parkin, D. Forman, F. Bray, Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 136, 359–386 (2015)

    Article  CAS  Google Scholar 

  2. R.L. Siegel, K.D. Miller, A. Jemal, Cancer statistics, 2016. CA Cancer J. Clin. 66, 7–30 (2016)

    Article  PubMed  Google Scholar 

  3. R. Sankaranarayanan, R. Swaminathan, K. Jayant, H. Brenner, An overview of cancer survival in Africa, Asia, the Caribbean and Central America: the case for investment in cancer health services. IARC Sci. Publ. 162, 257–291 (2011)

    Google Scholar 

  4. I. Cass, B.Y. Karlan, Ovarian cancer symptoms speak out – but what are they really saying? J. Natl. Cancer Inst. 102, 211–212 (2010)

    Article  PubMed  Google Scholar 

  5. K.A. Lowe, V.M. Chia, A. Taylor, C. O’Malleye, M. Kelsh, M. Mohamed, F.S. Mowat, B. Goff, An international assessment of ovarian cancer incidence and mortality. Gynecol. Oncol. 130, 107–114 (2013)

    Article  PubMed  Google Scholar 

  6. R. De Angelis, M. Sant, P.M. Coleman, S. Francisci, P. Baili, D. Pierannunzio, A. Trama, O. Visser, H. Brenner, E. Ardanaz, M. Bielska-Lasota, G. Engholm, A. Nennecke, S. Siesling, F. Berrino, R. Capocaccia, EUROCARE-5 working group, cancer survival in Europe 1999-2007 by country and age: results of Eurocare-5 – a population-based study. Lancet Oncol. 15, 23–34 (2014)

    Article  PubMed  Google Scholar 

  7. F. Dayyani, S. Uhlig, B. Colson, K. Simon, V. Rolny, D. Morgenstern, M. Schlumbrecht, Diagnostic performance of risk of ovarian malignancy algorithm against CA125 and HE4 in connection with ovarian cancer: a meta-analysis. Int. J. Gynecol. Cancer 26, 1586–1593 (2016)

    Article  PubMed  Google Scholar 

  8. J.L. Walker, C.B. Powell, L.M. Chen, J. Carter, V.L. Bae, L.P. Parker, M.E. Borowsky, R.K. Gibb, Society of Gynecologic Oncology recommendations for the prevention of ovarian cancer. Cancer 121, 2108–2120 (2015)

    Article  PubMed  Google Scholar 

  9. http://www.gopubmed.com/web/gopubmed/. Accessed 30 August 2016

  10. S. Lambrechts, D. Smeets, M. Moisse, E.I. Braicu, A. Vanderstichele, H. Zhao, E. Van, E. Berns, J. Sehouli, R. Zeillinger, S. Darb-Esfahani, D. Cacsire, D. Lambrechts, I. Vergote, Genetic heterogeneity after first-line chemotherapy in high-grade serous ovarian cancer. Eur. J. Cancer 53, 51–64 (2016)

    Article  CAS  PubMed  Google Scholar 

  11. M. Petrillo, C. Nero, G. Amadio, D. Gallo, A. Fagotti, G. Scambia, Targeting the hallmarks of ovarian cancer: the big picture. Gynecol. Oncol. 142, 176–183 (2016)

    Article  CAS  PubMed  Google Scholar 

  12. C. Santos, R. Sanz-Pamplona, E. Nadal, J. Grasselli, S. Pernas, R. Dienstmann, V. Moreno, J. Tabernero, R. Salazar, Intrinsic cancer subtypes-next steps into personalized medicine. Cell. Oncol. 38, 3–16 (2015)

    Article  Google Scholar 

  13. A. Zaal, W.J. Peyrot, P.M. Berns, M.E. van der Burg, J.H. Veerbeek, J.B. Trimbos, I. Cadron, P.J. van Diest, W.N. van Wieringen, O. Krijgsman, G.A. Meijer, J.M. Piek, P.J. Timmers, I. Vergote, R.H. Verheijen, B. Ylstra, R.P. Zweemer, EORTC GCG translational research group, genomic aberrations relate early and advanced stage ovarian cancer. Cell. Oncol. 35, 181–188 (2012)

    Article  Google Scholar 

  14. M.E. Maradeo, P. Cairns, Translational application of epigenetic alterations: ovarian cancer as a model. FEBS Lett. 585, 2112–2120 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. J.J. Wallbillich, B. Forde, L.J. Havrilesky, D.E. Cohn, A personalized paradigm in the treatment of platinum-resistant ovarian cancer–a cost utility analysis of genomic-based versus cytotoxic therapy. Gynecol. Oncol. 142, 144–149 (2016)

    Article  CAS  PubMed  Google Scholar 

  16. B.V. Chakravarthi, S. Nepal, S. Varambally, Genomic and epigenomic alterations in cancer. Am. J. Pathol. 186, 1724–1735 (2016)

    Article  CAS  PubMed  Google Scholar 

  17. R.J. Kurman, I.-M. Shih, The origin and pathogenesis of epithelial ovarian cancer-a proposed unifying theory. Am. J. Surg. Pathol. 34, 433–443 (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  18. N.N. Nik, R. Vang, I.M. Shih, R.J. Kurman, Origin and pathogenesis of pelvic (ovarian, tubal, and primary peritoneal) serous carcinoma. Annu. Rev. Pathol. 9, 27–45 (2014)

    Article  CAS  PubMed  Google Scholar 

  19. N. Colombo, M. Peiretti, A. Garbi, S. Carinelli, C. Marini, C. Sessa, Non-epithelial ovarian cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 23, 20–26 (2012)

    Google Scholar 

  20. W.D. Foulkes, M. Gore, W.G.M. Cluggage, Rare non-epithelial ovarian neoplasms: pathology, genetics and treatment. Gynecol. Oncol. 142, 190–198 (2016)

    Article  CAS  PubMed  Google Scholar 

  21. M. Köbel, S.E. Kalloger, D.G. Huntsman, J.L. Santos, K.D. Swenerton, J.D. Seidman, C.B. Gilks, Cheryl Brown ovarian cancer outcomes unit of the British Columbia Cancer Agency, Vancouver BC. Differences in tumor type in low-stage versus high-stage ovarian carcinomas. Int. J. Gynecol. Pathol. 29, 203–211 (2010)

    Article  PubMed  Google Scholar 

  22. J. Prat, New insights into ovarian cancer pathology. Ann. Oncol. 23 (Suppl 10), 111–117 (2012)

  23. A. Halon, V. Materna, M. Drag-Zalesinska, E. Nowak-Markwitz, T. Gansukh, P. Donizy, M. Spaczynski, M. Zabel, M. Dietel, H. Lage, P. Surowiak, Estrogen receptor alpha expression in ovarian cancer predicts longer overall survival. Pathol. Oncol. Res. 17, 511–518 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. R.J. Kurman, I.M. Shih, The dualistic model of ovarian carcinogenesis: revisited, revised, and expanded. Am. J. Pathol. 186, 733–747 (2016)

    Article  PubMed  Google Scholar 

  25. Cancer Genome Atlas Research Network, Integrated genomic analyses of ovarian carcinoma. Nature 474, 609–615 (2011)

    Article  CAS  Google Scholar 

  26. A. Bamias, S. Pignata, E. Pujade-Lauraine, Angiogenesis: a promising therapeutic target for ovarian cancer. Crit. Rev. Oncol. Hematol. 84, 314–326 (2012)

    Article  CAS  PubMed  Google Scholar 

  27. N.G. Gavalas, M. Liontos, S.P. Trachana, T. Bagratuni, C. Arapinis, C. Liacos, M.A. Dimopoulos, A. Bamias, Angiogenesis-related pathways in the pathogenesis of ovarian cancer. Int. J. Mol. Sci. 14, 15885–15909 (2013)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. J. Farley, W.E. Brady, V. Vathipadiekal, H.A. Lankes, R. Coleman, M.A. Morgan, R. Mannel, S.D. Yamada, D. Mutch, W.H. Rodgers, M. Birrer, D.M. Gershenson, Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study. Lancet Oncol. 14, 134–140 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. L.M. Landrum, J. Java, C.A. Mathews, G.S. Lanneau, L.J. Copeland, D.K. Armstrong, J.L. Walker, Prognostic factors for stage III epithelial ovarian cancer treated with intraperitoneal chemotherapy: a gynecologic oncology group study. Gynecol. Oncol. 130, 12–18 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  30. I. Romero, R.C. Bast Jr., Minireview: human ovarian cancer: biology, current management, and paths to personalizing therapy. Endocrinology 153, 1593–1602 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Y. Yang-Hartwich, M.G. Soteras, Z.P. Lin, J. Holmberg, N. Sumi, V. Craveiro, M. Liang, E. Romanoff, J. Bingham, F. Garofalo, A. Alvero, G. Mor, p53 protein aggregation promotes platinum resistance in ovarian cancer. Oncogene 34, 3605–3616 (2015)

    Article  CAS  PubMed  Google Scholar 

  32. O. Caron, Oncogenetics in the management of ovarian cancer: state-of-the art. Gynecol. Obstet. Fertil. 43, 335–337 (2015)

    Article  CAS  PubMed  Google Scholar 

  33. A.A. Ahmed, D. Etemadmoghadam, J. Temple, A.G. Lynch, M. Riad, R. Sharma, C. Stewart, S. Fereday, C. Caldas, A. Defazio, D. Bowtell, J.D. Brenton, Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary. J. Med. Surg. Pathol. 221, 49–56 (2010)

    CAS  Google Scholar 

  34. R. Wu, S.J. Baker, T.C. Hu, K.M. Norman, E.R. Fearon, K.R. Cho, Type I to type II ovarian carcinoma progression: mutant Trp53 or Pik3ca confers a more aggressive tumor phenotype in a mouse model of ovarian cancer. Am. J. Pathol. 182, 1391–1399 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. J. Prat, Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch. 460, 237–249 (2012)

    Article  PubMed  Google Scholar 

  36. R.D.A. Weren, A.R. Mensenkamp, M. Simons, A. Eijkelenboom, A.S. Sie, H. Ouchene, M. van Asseldonk, E.B. Gomez-Garcia, M.J. Blok, J.A. de Hullu, M.R. Nelen, A. Hoischen, J. Bulten, B.B.J. Tops, N. Hoogerbrugge, M.J.L. Ligtenberg, Novel BRCA1 and BRCA2 tumor test as basis for treatment decisions and referral for genetic counselling of patients with ovarian carcinomas. Hum. Mutat. (2016). doi:10.1002/humu.23137

    PubMed  PubMed Central  Google Scholar 

  37. K.P. Pennington, T. Walsh, M.I. Harrell, M.K. Lee, C.C. Pennil, M.H. Rendi, A. Thornton, B.M. Norquist, S. Casadei, A.S. Nord, K.J. Agnew, C.C. Pritchard, S. Scroggins, R.L. Garcia, M. King, E.M. Swisher, Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin. Cancer Res. 20, 764–775 (2014)

    Article  CAS  PubMed  Google Scholar 

  38. J.R. McLaughlin, B. Rosen, J. Moody, T. Pal, I. Fan, P.A. Shaw, H.A. Risch, T.A. Sellers, P. Sun, S.A. Narod, Long-term ovarian cancer survival associated with mutation in BRCA1 or BRCA2. J. Natl. Cancer Inst. 105, 141–148 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. S.B. Kaye, J. Lubinski, U. Matulonis, J.E. Ang, C. Gourley, B.Y. Karlan, A. Amnon, K.M. BellMcGuinn, L.M. Chen, M. Friedlander, T. Safra, I. Vergote, M. Wickens, E.S. Lowe, J. Carmichael, B. Kaufman, I.I. Phase, Open-label, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADP-ribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer. J. Clin. Oncol. 30, 372–379 (2012)

    Article  CAS  PubMed  Google Scholar 

  40. J.F. Liu, P.A. Konstantinopoulos, U.A. Matulonis, PARP inhibitors in ovarian cancer: current status and future promise. Gynecol. Oncol. 133, 362–369 (2014)

    Article  CAS  PubMed  Google Scholar 

  41. Y. Hirotsu, H. Nakagomi, I. Sakamoto, K. Amemiya, H. Mochizuki, M. Omata, Detection of BRCA1 and BRCA2 germline mutations in Japanese population using next-generation sequencing. Mol. Genet. Genomic. Med. 3, 121–129 (2015)

    Article  CAS  PubMed  Google Scholar 

  42. C.M. Strom, S. Rivera, C. Elzinga, T. Angeloni, S.H. Rosenthal, D. Goos-Root, M. Siaw, J. Platt, C. Braastadt, L. Cheng, D. Ross, W. Sun, Development and validation of a next-generation sequencing assay for BRCA1 and BRCA2 variants for the clinical laboratory. PLoS One 10, e0136419 (2015)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. J.B. Hiatt, C.C. Pritchard, S.J. Salipante, B.J. O'Roak, J. Shendure, Single molecule molecular inversion probes for targeted, high-accuracy detection of low-frequency variation. Genome Res. 23, 843–854 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. P. Bottoni, R. Scatena, The role of CA 125 as tumor marker: biochemical and clinical aspects. Adv. Exp. Med. Biol. 867, 229–244 (2015)

    Article  PubMed  Google Scholar 

  45. V.A. Moyer, Screening for ovarian cancer: US preventive services task force reaffirmation recommendation statement. Ann. Intern. Med. 157, 900–904 (2012)

    Article  PubMed  Google Scholar 

  46. S.S. Buys, E. Partridge, A. Black, C.C. Johnson, L. Lamerato, C. Isaacs, D.J. Reding, R.T. Greenlee, L.A. Yokochi, B. Kessel, E.D. Crawford, T.R. Church, G.L. Andriole, J.L. Weissfeld, M.N. Fouad, D. Chia, B. O'Brien, L.R. Ragard, J.D. Clapp, J.M. Rathmell, T.L. Riley, P. Hartge, P.F. Pinsky, C.S. Zhu, G. Izmirlian, B.S. Kramer, A.B. Miller, J.L. Xu, P.C. Prorok, J.K. Gohagan, C.D. Berg, PLCO Project Team, Effect of screening on ovarian cancer mortality: the prostate, lung, colorectal and ovarian (PLCO) cancer screening randomized controlled trial. JAMA 305, 2295–2303 (2011)

    Article  CAS  PubMed  Google Scholar 

  47. I.J. Jacobs, U. Menon, A. Ryan, A. Gentry-Maharaj, M. Burnell, J.K. Kalsi, N.N. Amso, S. Apostolidou, E. Benjamin, D. Cruickshank, D.N. Crump, S.K. Davies, A. Dawnay, S. Dobbs, G. Fletcher, J. Ford, K. Godfrey, R. Gunu, M. Habib, R. Hallett, J. Herod, H. Jenkins, C. Karpinskyj, S. Leeson, S.J. Lewis, W.R. Liston, A. Lopes, T. Mould, J. Murdoch, D. Oram, D.J. Rabideau, K. Reynolds, I. Scott, M.W. Seif, A. Sharma, N. Singh, J. Taylor, F. Warburton, M. Widschwendter, K. Williamson, R. Woolas, L. Fallowfield, A.J. McGuire, S. Campbell, M. Parmar, S.J. Skates, Ovarian cancer screening and mortality in the UK collaborative trial of ovarian cancer screening (UKCTOCS): a randomised controlled trial. Lancet 387, 945–956 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  48. B.M. Nolen, A.E. Lokshin, Biomarker testing for ovarian cancer: clinical utility of multiplex assays. Mol. Diagn. Ther. 17, 139–146 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. R.G. Moore, M.C. Miller, P. Disilvestro, L.M. Landrum, W. Gajewski, J.J. Ball, S.J. Skates, Evaluation of the diagnostic accuracy of the risk of ovarian malignancy algorithm in women with a pelvic mass. Obstet. Gynecol. 118, 280 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  50. T. Van Gorp, I. Cadron, E. Despierre, A. Daemen, K. Leunen, F. Amant, D. Timmerman, B. De Moor, I. Vergote, HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the risk of ovarian malignancy algorithm. Brit. J. Cancer 104, 863–870 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Y. Xu, R. Zhong, J. He, R. Ding, H. Lin, Y. Deng, L. Zhou, X. Li, J. Jiang, Y. Bao, X. Luo, C. Duan, Modification of cut-off values for HE4, CA125 and the ROMA algorithm for early-stage epithelial ovarian cancer detection: results from 1021 cases in South China. Clin. Biochem. 49, 32–40 (2016)

    Article  PubMed  Google Scholar 

  52. M.R. Andersen, B.A. Goff, K.A. Lowe, N. Scholler, L. Bergan, C.W. Drescher, P. Paley, N. Urban, Use of a symptom index, CA125, and HE4 to predict ovarian cancer. J. Gynecol. Oncol. 116, 378–383 (2010)

    Article  Google Scholar 

  53. T. Edgell, G. Martin-Roussety, G. Barker, D.J. Autelitano, D. Allen, P. Grant, G.E. Rice, Phase II biomarker trial of a multimarker diagnostic for ovarian cancer. J. Cancer Res. Clin. Oncol. 136, 1079–1088 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Z. Yurkovetsky, S. Skates, A. Lomakin, B. Nolen, T. Pulsipher, F. Modugno, J. Marks, A. Godwin, E. Gorelik, I. Jacobs, U. Menon, K. Lu, D. Badgwell, R.C. Bast Jr., A.E. Lokshin, Development of a multimarker assay for early detection of ovarian cancer. J. Clin. Oncol. 28, 2159–2166 (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  55. E. Kipps, D.S. Tan, S.B. Kaye, Meeting the challenge of ascites in ovarian cancer: new avenues for therapy and research. Nat. Rev. Cancer 13, 273–282 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. K.L. Terry, H. Schock, R.T. Fortner, A. Hüsing, R.N. Fichorova, H.S. Yamamoto, A.F. Vitonis, T. Johnson, K. Overvad, A. Tjønneland, M.C. Boutron-Ruault, S. Mesrine, G. Severi, L. Dossus, S. Rinaldi, H. Boeing, V. Benetou, P. Lagiou, A. Trichopoulou, V. Krogh, E. Kuhn, S. Panico, H.B. Bueno-de-Mesquita, N.C. Onland-Moret, P.H. Peeters, I.T. Gram, E. Weiderpass, E.J. Duell, M.J. Sanchez, E. Ardanaz, N. Etxezarreta, C. Navarro, A. Idahl, E. Lundin, K. Jirström, J. Manjer, N.J. Wareham, K.T. Khaw, K. Smith Byrne, R.C. Travis, M.J. Gunter, M.A. Merritt, E. Riboli, D. Cramer, R. Kaaks, A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort. Clin. Cancer Res. 22, 1078–10432 (2016)

    Article  CAS  Google Scholar 

  57. P. Vinken, S. Starckx, E. Barale-Thomas, A. Looszova, M. Sonee, N. Goeminne, L. Versmissen, K. Buyens, A. Lampo, Tissue Kim-1 and urinary clusterin as early indicators of cisplatin-induced acute kidney injury in rats. Toxicol. Pathol. 40, 1049–1062 (2012)

    Article  PubMed  CAS  Google Scholar 

  58. Z. Zhang, D.W. Chan, The road from discovery to clinical diagnostics: lessons learned from the first FDA-cleared in vitro diagnostic multivariate index assay of proteomic biomarkers. Cancer Epidem. Biomar. 19, 2995–2999 (2010)

    Article  CAS  Google Scholar 

  59. R.W. Miller, A. Smith, C.P. DeSimone, L. Seamon, S. Goodrich, I. Podzielinski, L. Sokoll, J.R. van Nagell Jr., Z. Zhang, F.R. Ueland, Performance of the American College of Obstetricians and Gynecologists' ovarian tumor referral guidelines with a multivariate index assay. Obstet. Gynecol. 117, 1298–1306 (2011)

    Article  Google Scholar 

  60. B.H. Shadfan, A.R. Simmons, G.W. Simmons, A. Ho, J. Wong, K.H. Lu, R.C. Bast, J.T. McDevitt, A multiplexable, microfluidic platform for the rapid quantitation of a biomarker panel for early ovarian cancer detection at the point-of-care. Cancer Prev. Res. 8, 37–48 (2015)

    Article  CAS  Google Scholar 

  61. Y.W. Kim, S.M. Bae, H. Lim, Y.J. Kim, W.S. Ahn, Development of multiplexed bead-based immunoassays for the detection of early stage ovarian cancer using a combination of serum biomarkers. PLoS One 7, e44960 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. S. Kato, L. Abarzua-Catalan, C. Trigo, A. Delpiano, C. Sanhueza, K. García, C. Ibañez, K. Hormazábal, D. Diaz, J. Brañes, E. Castellón, E. Bravo, G. Owen, M. Cuello, Leptin stimulates migration and invasion and maintains cancer stem-like properties in ovarian cancer cells: an explanation for poor outcomes in obese women. Oncotarget 6, 21100–21119 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  63. N.M.A. White, T.F. Chow, S. Mejia-Guerrero, M. Diamandis, Y. Rofael, H. Faragalla, G.M. Yousef, Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer. Brit. J. Cancer 102, 1244–1253 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. M.A.H. El Sherbini, M.M. Sallam, E.A.K. Shaban, A.H. El-Shalakany, Diagnostic value of serum kallikrein-related peptidases 6 and 10 versus CA125 in ovarian cancer. Int. J. Gynecol. Cancer 21, 625–632 (2011)

    Article  PubMed  Google Scholar 

  65. S.C.L. Koh, C.Y. Huak, D. Lutan, J. Marpuang, S. Ketut, N.G. Budiana, N.K.H. Hoan, Combined panel of serum human tissue kallikreins and CA-125 for the detection of epithelial ovarian cancer. J. Gynecol. Oncol. 23, 175–181 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. M.K. Siu, H.Y. Chan, D.S. Kong, E.S. Wong, O.G. Wong, H.Y. Ngan, K.F. Tam, H. Zhang, Z. Li, Q.K. Chan, S.W. Tsao, p21-activated kinase 4 regulates ovarian cancer cell proliferation, migration, and invasion and contributes to poor prognosis in patients. Proc. Natl. Acad. Sci. U. S. A. 107, 18622–18627 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. X. Xia, Q. Ma, X. Li, T. Ji, P. Chen, H. Xu, S. Liao, Z. Han, R. Liu, T. Zhu, S. Wang, G. Xu, L. Meng, J. Zhou, D. Ma, Cytoplasmic p21 is a potential predictor for cisplatin sensitivity in ovarian cancer. BMC Cancer 11, 399 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. K. Wurz, R.L. Garcia, B.A. Goff, P.S. Mitchell, J.H. Lee, M. Tewari, E.M. Swisher, MiR-221 and MiR-222 alterations in sporadic ovarian carcinoma: relationship to CDKN1B, CDKNIC and overall survival. Genes Chromosom. Cancer 49, 577–584 (2010)

    CAS  PubMed  PubMed Central  Google Scholar 

  69. L. Szabova, C. Yin, S. Bupp, T.M. Guerin, J.J. Schlomer, D.B. Householder, M.L. Baran, M. Yi, Y. Song, W. Sun, J.E. McDunn, Perturbation of Rb, p53, and Brca1 or Brca2 cooperate in inducing metastatic serous epithelial ovarian cancer. Cancer Res. 72, 4141–4153 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. K. Avraam, K. Pavlakis, C. Papadimitriou, T. Vrekoussis, T. Panoskaltsis, I. Messini, E. Patsouris, The prognostic and predictive value of ERCC-1, p53, bcl-2 and bax in epithelial ovarian cancer. Eur. J. Gynaecol. Oncol. 32, 516–520 (2010)

    Google Scholar 

  71. F. Kong, C. Sun, Z. Wang, L. Han, D. Weng, Y. Lu, G. Chen, miR-125b confers resistance of ovarian cancer cells to cisplatin by targeting pro-apoptotic Bcl-2 antagonist killer 1. J. Huazhong Univ. Sci. Technolog. Med. Sci. 31, 543–549 (2011)

    Article  CAS  PubMed  Google Scholar 

  72. S. Lawicki, G.E. Będkowska, E. Gacuta-Szumarska, M. Szmitkowski, The plasma concentration of VEGF, HE4 and CA125 as a new biomarkers panel in different stages and sub-types of epithelial ovarian tumors. J. Ovarian Res. 6, 1 (2013)

    Article  CAS  Google Scholar 

  73. M.R. Russell, M.J. Walker, A.J. Williamson, A. Gentry-Maharaj, A. Ryan, J. Kalsi, S. Skates, A. D'Amato, C. Dive, M. Pernemalm, P.C. Humphryes, Protein Z: a putative novel biomarker for early detection of ovarian cancer. Int. J. Cancer 138, 2984–2992 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. K.M. Nieman, H.A. Kenny, C.V. Penicka, A. Ladanyi, R. Buell-Gutbrod, M.R. Zillhardt, I.L. Romero, M.S. Carey, G.B. Mills, G.S. Hotamisligil, S.D. Yamada, Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat. Med. 17, 1498–1503 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. M. Zou, X. Zhang, C. Xu, IL6-induced metastasis modulators p-STAT3, MMP-2 and MMP-9 are targets of 3,3′-diindolylmethane in ovarian cancer cells. Cell. Oncol. 39, 47–57 (2016)

    Article  CAS  Google Scholar 

  76. S.J. Bensinger, H.R. Christofk, New aspects of the Warburg effect in cancer cell biology, Semin. Cell. Dev. Biol. 23, 352–361 (2012)

    Article  CAS  Google Scholar 

  77. M.V. Liberti, J.W. Locasale, The Warburg effect: how does it benefit cancer cells? Trends Biochem. Sci. 41, 211–218 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. A.J. Levine, A.M. Puzio-Kuter, The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science 330, 1340–1344 (2010)

    Article  CAS  PubMed  Google Scholar 

  79. M.G. Vander Heiden, J.W. Locasale, K.D. Swanson, H. Sharfi, G.J. Heffron, D. Amador-Noguez, H.R. Christofk, G. Wagner, J.D. Rabinowitz, J.M. Asara, L.C. Cantley, Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science 329, 1492–1499 (2010)

    Article  CAS  PubMed  Google Scholar 

  80. M.Y. Fong, J. McDunn, S.S. Kakar, Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer. PLoS One 6, e19963 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. A. Beach, H.G. Zhang, M.Z. Ratajczak, S.S. Kakar, Exosomes: an overview of biogenesis, composition and role in ovarian cancer. J. Ovarian Res. 7, 14 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. A. Caivano, F. La Rocca, V. Simeon, M. Girasole, S. Dinarelli, I. Laurenzana, A. De Stradis, L. De Luca, S. Trino, A. Traficante, G. D’Arena, G. Mansueto, O. Villani, G. Pietrantuono, L. Laurenti, L. Del Vecchio, P. Musto, MicroRNA-155 in serum-derived extracellular vesicles as a potential biomarker for hematologic malignancies - a short report. Cell. Oncol. (2016) doi:10.1007/s13402-016-0300-x

    Google Scholar 

  83. L. Balaj, R. Lessard, L. Dai, Y.J. Cho, S.L. Pomeroy, X.O. Breakefield, J. Skog, Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat. Commun. 2, 180 (2011)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. A. Waldenstrom, N. Genneback, U. Hellman, G. Ronquist, Cardiomyocyte microvesicles contain DNA/RNA and convey biological messages to target cells. PLoS One 7, e34653 (2012)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. C.A. Maguire, L. Balaj, S. Sivaraman, M.H. Crommentuijn, M. Ericsson, L. Mincheva-Nilsson, V. Baranov, D. Gianni, B.A. Tannous, M. Sena-Esteves, X.O. Breakefield, Microvesicle-associated AAV vector as a novel gene delivery system. Mol. Ther. 20, 960–971 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. C. Escrevente, S. Keller, P. Altevogt, J. Costa, Interaction and uptake of exosomes by ovarian cancer cells. BMC Cancer 11, 108 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. K.D.P. Dorayappan, J.J. Wallbillich, D.E. Cohn, K. Selvendiran, The biological significance and clinical applications of exosomes in ovarian cancer. Gynecol. Oncol. 142, 199–205 (2016)

    Article  CAS  PubMed  Google Scholar 

  88. A. Bobrie, M. Colombo, G. Raposo, C. Thery, Exosome secretion: molecular mechanisms and roles in immune responses. Traffic 12, 1659–1668 (2011)

    Article  CAS  PubMed  Google Scholar 

  89. I. Nazarenko, S. Rana, A. Baumann, J. McAlear, A. Hellwig, M. Trendelenburg, G. Lochnit, K.T. Preissner, M. Zöller, Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation. Cancer Res. 70, 1668–1678 (2010)

    Article  CAS  PubMed  Google Scholar 

  90. R. Cappellesso, A. Tinazzi, T. Giurici, F. Simonato, V. Guzzardo, L. Ventura, M. Crescenzi, S. Chiarelli, A. Fassina, Programmed cell death 4 and microRNA 21 inverse expression is maintained in cells and exosomes from ovarian serous carcinoma effusions. Cancer Cytopathol. 122, 685–693 (2014)

    Article  CAS  PubMed  Google Scholar 

  91. O. Vaksman, C. Tropé, B. Davidson, R. Reich, Exosome-derived miRNAs and ovarian carcinoma progression. Carcinogenesis 35, 2113–2120 (2014)

    Article  CAS  PubMed  Google Scholar 

  92. A. Liga, A.D.B. Vliegenthart, W. Oosthuyzen, J.W. Dear, M. Kersaudy-Kerhoas, Exosome isolation: a microfluidic road-map. Lab Chip 15, 2388–2394 (2015)

    Article  CAS  PubMed  Google Scholar 

  93. D. Hanahan, R.A. Weinberg, Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011)

    Article  CAS  PubMed  Google Scholar 

  94. R. Paduch, The role of lymphangiogenesis and angiogenesis in tumor metastasis. Cell. Oncol. 39, 397–410 (2016)

  95. L.H.A. Broersen, G.W. van Pelt, R.A.E.M. Tollenaar, W.E. Mesker, Clinical application of circulating tumor cells in breast cancer. Cell. Oncol. 37, 9–15 (2014)

    Article  CAS  Google Scholar 

  96. C. Van Berckelaer, A.J. Brouwers, D.J.E. Peeters, W. Tjalma, X.B. Trinh, P.A. van Dam, Current and future role of circulating tumor cells in patients with epithelial ovarian cancer. Eur. J. Surg. Oncol. (2016). doi:10.1016/j.ejso.2016.05.010

    PubMed  Google Scholar 

  97. C. Van Berckelaer, A.J. Brouwers, D.J. Peeters, W. Tjalma, X.B. Trinh, P.A. van Dam, Current and future role of circulating tumor cells in patients with epithelial ovarian cancer. Eur. J. Surg. Oncol. (2016). doi:10.1016/j.ejso.2016.05.010

    PubMed  Google Scholar 

  98. E. Obermayr, D.C. Castillo-Tong, D. Pils, P. Speiser, I. Braicu, T. Van Gorp, S. Mahner, J. Sehouli, I. Vergote, R. Zeillinger, Molecular characterization of circulating tumor cells in patients with ovarian cancer improves their prognostic significance—a study of the OVCAD consortium. Gynecol. Oncol. 128, 15–21 (2013)

    Article  CAS  PubMed  Google Scholar 

  99. E. Obermayr, F. Sanchez-Cabo, M.K.M. Tea, C.F. Singer, M. Krainer, M.B. Fischer, J. Sehouli, A. Reinthaller, R. Horvat, G. Heinze, D. Tong, Assessment of a six gene panel for the molecular detection of circulating tumor cells in the blood of female cancer patients. BMC Cancer 10, 666 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. K. Kolostova, M. Pinkas, A. Jakabova, E. Pospisilova, P. Svobodova, J. Spicka, M. Cegan, R. Matkowski, V. Bobek, Molecular characterization of circulating tumor cells in ovarian cancer. Am. J. Cancer Res. 6, 973–980 (2016)

    PubMed  PubMed Central  Google Scholar 

  101. K. Kolostova, R. Matkowski, M. Jędryka, K. Soter, M. Cegan, M. Pinkas, A. Jakabova, J. Pavlasek, J. Spicka, V. Bobek, The added value of circulating tumor cells examination in ovarian cancer staging. Am. J. Cancer Res. 5, 3363–3375 (2015)

    PubMed  PubMed Central  Google Scholar 

  102. R.R. Langley, I.J. Fidler, The seed and soil hypothesis revisited—the role of tumor-stroma interactions in metastasis to different organs. Int. J. Cancer 128, 2527–2535 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. E. Kolwijck, J. Kos, N. Obermajer, P.N. Span, C.M. Thomas, L.F. Massuger, F.C. Sweep, The balance between extracellular cathepsins and cystatin C is of importance for ovarian cancer. Eur. J. Clin. Investig. 40, 591–599 (2010)

    Article  CAS  Google Scholar 

  104. E. Lengyel, Ovarian cancer development and metastasis. Am. J. Pathol. 177, 1053–1064 (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  105. S.M. Khan, H.M. Funk, S. Thiolloy, T.L. Lotan, J. Hickson, G.S. Prins, C.W. Rinker-Schaeffer, In vitro metastatic colonization of human ovarian cancer cells to the omentum. Clin. Exp. Metastasis 27, 185–196 (2010)

    Article  PubMed  Google Scholar 

  106. M. Galea, G. Gauci, J. Calleja-Agius, P. Schembri-Wismayer, Peritoneal biomarkers in the early detection of ovarian cancer. Minerva. Ginecol. (2016, in press)

  107. R. Drake, A.W. Vogl, A.W.M. Mitchel, Gray's anatomy for students (Churchill Livingstone/Elsevier, Philadelphia, 2010)

    Google Scholar 

  108. U. Kucukgoz Gulec, S. Paydas, A.B. Guzel, S. Buyukkurt, G. Seydaoglu, M.A. Vardar, Comparative analysis of CA 125, ferritin, beta-2 microglobulin, lactic dehydrogenase levels in serum and peritoneal fluid in patients with ovarian neoplasia. Med. Oncol. 29, 2937–2943 (2012)

    Article  CAS  PubMed  Google Scholar 

  109. V.M. Peterson, C.M. Castro, J. Chung, N.C. Miller, A.V. Ullal, M.D. Castano, R.T. Penson, H. Lee, M.J. Birrer, R. Weissleder, Ascites analysis by a microfluidic chip allows tumor-cell profiling. Proc. Natl. Acad. Sci. U. S. A. 110, E4978–E4986 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. L.M. Amon, W. Law, M.P. Fitzgibbon, J.A. Gross, K. O'Briant, A. Peterson, C. Drescher, D.B. Martin, M. McIntosh, Integrative proteomic analysis of serum and peritoneal fluids helps identify proteins that are up-regulated in serum of women with ovarian cancer. PLoS One 5, e11137 (2010)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. M.A. Dawson, T. Kouzarides, Cancer epigenetics: from mechanism to therapy. Cell 150, 12–27 (2012)

    Article  CAS  PubMed  Google Scholar 

  112. H. Easwaran, H.C. Tsai, S.B. Baylin, Cancer epigenetics: tumor heterogeneity, plasticity of stem-like states, and drug resistance. Mol. Cell 54, 716–727 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. A. Ferraro, Altered primary chromatin structures and their implications in cancer development. Cell. Oncol. 39, 195–210 (2016)

    Article  Google Scholar 

  114. E. Heard, R.A. Martienssen, Transgenerational epigenetic inheritance: myths and mechanisms. Cell 157, 95–109 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. W.L. Tam, R.A. Weinberg, The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat. Med. 19, 1438–1449 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. J.S. You, P.A. Jones, Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell 22, 9–20 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. J. Tost, I.G. Gut, in Molecular Diagnostics (Third Edition), ed. by George P. Patrinos, Philip B. Danielson and Wilhelm J. Ansorge (Elsevier/Academic Press, Amsterdam, 2017), pp.103–139. doi:10.1016/B978-0-12-802971-8.00007-9

  118. T.E. Liggett, A. Melnikov, Q. Yi, C. Replogle, W. Hu, J. Rotmensch, A. Kamat, A.K. Sood, V. Levenson, Distinctive DNA methylation patterns of cell-free plasma DNA in women with malignant ovarian tumors. Gynecol. Oncol. 120, 113–120 (2011)

    Article  CAS  PubMed  Google Scholar 

  119. C. Marsit, B. Christensen, Epigenetic Alterations in Oncogenesis, ed. by Adam R. Karpf (Springer, Berlin Heidelberg New York) (2013), pp. 233–252

  120. L.M.S. Seeber, P.J. Van Diest. Epigenetics in Cancer Epigenetics: Methods and Protocols, ed. by G. D. Ramona and V. Mukesh (Springer, Berlin Heidelberg New York, 2012), pp 253–269.

  121. J.A.T. Pepin, H. Cardenas, C. Moore, S. Condello, J. Guanglong, L. Yunlong, D. Matei, Epigenetic vulnerabilities in ovarian cancer. Cancer Res. 76, 4486–4486 (2016)

    Article  Google Scholar 

  122. M. Longacre, N.A. Snyder, G. Housman, M. Leary, K. Lapinska, S. Heerboth, A. Willbanks, S. Sarkar, A comparative analysis of genetic and epigenetic events of breast and ovarian cancer related to tumorigenesis. Int. J. Mol. Sci. 17, 759 (2016)

    Article  PubMed Central  Google Scholar 

  123. H. Mirzaei, F. Yazdi, R. Salehi, H.R. Mirzaei, SiRNA and epigenetic aberrations in ovarian cancer. J. Cancer Res. Ther. 12, 498–508 (2016)

    Article  CAS  PubMed  Google Scholar 

  124. M. Kaur, A. Singh, K. Singh, S. Gupta, M. Sachan, Development of a multiplex MethyLight assay for the detection of DAPK1 and SOX1 methylation in epithelial ovarian cancer in a north Indian population. Genes Genet. Syst. (2016). doi:10.1266/ggs.15-00051

    PubMed  Google Scholar 

  125. Y.P. Liao, L.Y. Chen, R.L. Huang, P.H. Su, M.W. Chan, C.C. Chang, M.H. Yu, P.H. Wang, M.S. Yen, K.P. Nephew, H.C. Lai, Hypomethylation signature of tumor-initiating cells predicts poor prognosis of ovarian cancer patients. Hum. Mol. Genet. 23, 1894–1906 (2014)

    Article  CAS  PubMed  Google Scholar 

  126. X. Lin, X. Shang, G. Manorek, S. Howell, Control of integrin expression and signaling by claudin-3 and claudin-4 in ovarian cancer. Cancer Res. 73, 211–211 (2013)

    Article  CAS  Google Scholar 

  127. Y.F. Huang, W.F. Cheng, Y.P. Wu, Y.M. Cheng, K.F. Hsu, C.Y. Chou, Circulating IGF system and treatment outcome in epithelial ovarian cancer. Endocr. Relat. Cancer 21, 217–229 (2014)

    Article  CAS  PubMed  Google Scholar 

  128. D.J. Marsh, J.S. Shah, A.J. Cole, Histones and their modifications in ovarian cancer–drivers of disease and therapeutic targets. Front Oncol. 4, 144 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  129. K.R. Davis, K.J. Flower, J.V. Borley, C.S.M. Wilhelm-Benartzi, Cell-free circulating tumor DNA methylation in high-grade serous ovarian cancer. Cancer Res. 76, 3154–3154 (2016)

    Article  Google Scholar 

  130. S.N. Akers, K. Moysich, W. Zhang, G. Collamat Lai, A. Miller, S. Lele, K. Odunsi, A.R. Karpf, LINE1 and Alu repetitive element DNA methylation in tumors and white blood cells from epithelial ovarian cancer patients. Gynecol. Oncol. 132, 462–467 (2014)

    Article  CAS  PubMed  Google Scholar 

  131. A. DiazLuis, A. Bardelli, Liquid biopsies: genotyping circulating tumor DNA. J. Clin. Oncol. 32, 579–586 (2014)

    Article  Google Scholar 

  132. H. Holger, M. Esteller, DNA methylation profiling in the clinic: applications and challenges. Nat. Rev. Genet. 13, 679–692 (2012)

    Article  CAS  Google Scholar 

  133. C. Montavon, B.S. Gloss, K. Warton, C.A. Barton, A.L. Statham, J.P. Scurry, B. Tabor, T.V. Nguyen, W. Qu, G. Samimi, N.F. Hacker, Prognostic and diagnostic significance of DNA methylation patterns in high grade serous ovarian cancer. Gynecol. Oncol. 124, 582–588 (2012)

    Article  CAS  PubMed  Google Scholar 

  134. F. Yin, X. Liu, D. Li, Q. Wang, W. Zhang, L. Li, Tumor suppressor genes associated with drug resistance in ovarian cancer (review). Oncol. Rep. 30, 3–10 (2013)

    CAS  PubMed  Google Scholar 

  135. B. Zhang, F.F. Cai, X.Y. Zhong, An overview of biomarkers for the ovarian cancer diagnosis. Eur. J. Obstet. Gynecol. 158, 119–123 (2011)

  136. B.L. Valle, E. Kuhn, D. Sidransky, R. Guerrero-Preston, DNA promoter hypermethylation of genes as potential diagnostic and prognostic biomarkers for ovarian cancer. Cancer Res. 75, 2960–2960 (2015)

    Article  Google Scholar 

  137. A. Dobrovic, T. Mikeska, K. Alsop, I. Candiloro, J. George, G. Mitchell, D. Bowtell, Constitutional BRCA1 methylation is a major predisposition factor for high-grade serous ovarian cancer. Cancer Res. 74, 290–290 (2014)

    Article  Google Scholar 

  138. O.A. Al-Shabanah, M.M. Hafez, Z.K. Hassan, M.M. Sayed-Ahmed, W.N. Abozeed, A. Alsheikh, S.S. Al-Rejaie, Methylation of SFRPs and APC genes in ovarian cancer infected with high risk human papillomavirus. Asian Pac. J. Cancer Prev. 15, 2719–2725 (2013)

    Article  Google Scholar 

  139. R. Bhagat, S. Chadaga, C.S. Premalata, G. Ramesh, C. Ramesh, V.R. Pallavi, L. Krishnamoorthy, Aberrant promoter methylation of the RASSF1A and APC genes in epithelial ovarian carcinoma development. Cell. Oncol. 35, 473–479 (2012)

    Article  CAS  Google Scholar 

  140. V. Taucher, H. Mangge, J. Haybaeck, Non-coding RNAs in pancreatic cancer: challenges and opportunities for clinical application. Cell. Oncol. 39, 295–318 (2016)

    Article  CAS  Google Scholar 

  141. M. Vitiello, A. Tuccoli, L. Poliseno, Long non-coding RNAs in cancer: implications for personalized therapy. Cell. Oncol. 38, 17–28 (2015)

    Article  CAS  Google Scholar 

  142. M.D. Jansson, A.H. Lund, MicroRNA and cancer. Mol. Oncol. 6, 590–610 (2012)

    Article  CAS  PubMed  Google Scholar 

  143. M. Acunzo, G. Romano, D. Wernicke, C.M. Croce, MicroRNA and cancer–a brief overview. Adv. Biol. Regul. 57, 1–9 (2015)

    Article  CAS  PubMed  Google Scholar 

  144. L. Ayaz, F. Cayan, Ş. Balci, A. Görür, S. Akbayir, H. YıldırımYaroğlu, N. DoğruerUnal, L. Tamer, Circulating microRNA expression profiles in ovarian cancer. J. Obstet. Gynaecol. 4, 620–624 (2014)

    Article  CAS  Google Scholar 

  145. S. Zhang, Z. Lu, A.K. Unruh, C. Ivan, K.A. Baggerly, G.A. Calin, Z. Li, R.C. Bast Jr., X.F. Le, Clinically relevant microRNAs in ovarian cancer. Mol. Cancer Res. 13, 393–401 (2015)

    Article  CAS  PubMed  Google Scholar 

  146. M. Bagnoli, L. De Cecco, A. Granata, R. Nicoletti, E. Marchesi, P. Alberti, B. Valeri, M. Libra, M. Barbareschi, F. Raspagliesi, D. Mezzanzanica, S. Canevari, Identification of a chrXq27.3 microRNA cluster associated with early relapse in advanced stage ovarian cancer patients. Oncotarget 2, 1265–1278 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  147. S.F. Hausler, A. Keller, P.A. Chandran, K. Ziegler, K. Zipp, S. Heuer, M. Krockenberger, J.B. Engel, A. Hönig, M. Scheffler, J. Dietl, J. Wischhusen, Whole blood-derived miRNA profiles as potential new tools for ovarian cancer screening. Br. J. Cancer 103, 693–700 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Y.W. Chung, H.S. Bae, J.Y. Song, J.K. Lee, N.W. Lee, T. Kim, K.W. Lee, Detection of microRNA as novel biomarkers of epithelial ovarian cancer from the serum of ovarian cancer patients. Int. J. Gynecol. Cancer 23, 673–679 (2013)

    Article  PubMed  Google Scholar 

  149. H. Zheng, L. Zhang, Y. Zhao, D. Yang, F. Song, Y. Wen, Q. Hao, Z. Hu, W. Zhang, K. Chen, Plasma miRNAs as diagnostic and prognostic biomarkers for ovarian cancer. PLoS One 8, e77853 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. I. Shapira, M. Oswald, J. Lovecchio, H. Khalili, A. Menzin, J. Whyte, L. Dos Santos, S. Liang, T. Bhuiya, M. Keogh, C. Mason, Circulating biomarkers for detection of ovarian cancer and predicting cancer outcomes. Br. J. Cancer 110, 976–983 (2014)

    Article  CAS  PubMed  Google Scholar 

  151. C.W. Kan, V.M. Howell, M.A. Hahn, D.J. Marsh, Genomic alterations as mediators of miRNA dysregulation in ovarian cancer. Genes Chromosom. Cancer 54, 1–19 (2015)

    Article  CAS  PubMed  Google Scholar 

  152. R. Langhe, L. Norris, F.A. Saadeh, G. Blackshields, R. Varley, A. Harrison, N. Gleeson, C. Spillane, C. Martin, D.M. O'Donnell, T. D'Arcy, J. O'Leary, S. O'Toole, A novel serum microRNA panel to discriminate benign from malignant ovarian disease. Cancer Lett. 356, 628–636 (2015)

    Article  CAS  PubMed  Google Scholar 

  153. S. Leskelä, L.J. Leandro-García, M. Mendiola, J. Barriuso, L. Inglada-Pérez, I. Muñoz, B. Martínez-Delgado, A. Redondo, J. de Santiago, M. Robledo, D. Hardisson, The miR-200 family controls β-tubulin III expression and is associated with paclitaxel-based treatment response and progression-free survival in ovarian cancer patients. Endocr. Relat. Cancer 18, 85–95 (2011)

    Article  PubMed  CAS  Google Scholar 

  154. S. Marchini, D. Cavalieri, R. Fruscio, E. Calura, D. Garavaglia, I.F. Nerini, C. Mangioni, G. Cattoretti, L. Clivio, L. Beltrame, D. Katsaros, Association between miR-200c and the survival of patients with stage I epithelial ovarian cancer: a retrospective study of two independent tumour tissue collections. Lancet Oncol. 12, 273–285 (2011)

    Article  CAS  PubMed  Google Scholar 

  155. K. Nakamura, K. Sawada, A. Yoshimura, Y. Kinose, E. Nakatsuka, T. Kimura, Clinical relevance of circulating cell-free microRNAs in ovarian cancer. Mol. Cancer 15, 48 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  156. J. Zhou, G. Gong, H. Tan, F. Dai, X. Zhu, Y. Chen, J. Wang, Y. Liu, P. Chen, X. Wu, J. Wen, Urinary microRNA-30a-5p is a potential biomarker for ovarian serous adenocarcinoma. Oncol. Rep. 33, 2915–2923 (2015)

    CAS  PubMed  Google Scholar 

  157. Y. Chen, L. Zhang, Q. Hao, Candidate microRNA biomarkers in human epithelial ovarian cancer: systematic review profiling studies and experimental validation. Cancer Cell Int. 13, 86 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We are grateful to Pr. Fourtassi Maryam, associate professor of physical medicine and rehabilitation at the Medical School of Oujda-Morocco, for her constant encouragement and to Pr. SELLAM Amar for revising the English of the manuscript.

Author information

Authors and Affiliations

  1. Faculty of Medicine and Pharmacy, Oujda, Morocco

    Khalid El Bairi

  2. Independent Research Team in Cancer Biology and Bioactive Compounds, Mohammed 1st University, Oujda, Morocco

    Khalid El Bairi

  3. Department of Biochemistry, Healthcare Molecular and Diagnostic Laboratory, Hyderabad, Pakistan

    Abdul Hafeez Kandhro

  4. Laboratory of Medical Biochemistry, Ibn Rochd University Hospital, Annaba, Algeria

    Adel Gouri

  5. Laboratory of Biology and Health, URAC-34, Faculty of Science Ben Msik, University Hassan II, Mohammedia, Casablanca, Morocco

    Wafaa Mahfoud

  6. Labomac IVF Centers and Clinical Laboratory Medicine, Casablanca, Morocco

    Noureddine Louanjli

  7. IVF center IRIFIV, Clinique des Iris, Casablanca, Morocco

    Brahim Saadani

  8. Department of Medical Oncology, Mohamed 1st University Hospital, Oujda, Morocco

    Said Afqir

  9. Equipe de Recherche ONCOGYMA, Faculty of Medicine, Pathology Department, National Institute of Oncology, Université Mohamed V, Rabat, Morocco

    Mariam Amrani

Authors
  1. Khalid El Bairi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abdul Hafeez Kandhro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adel Gouri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wafaa Mahfoud
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Noureddine Louanjli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Brahim Saadani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Said Afqir
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mariam Amrani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Khalid El Bairi.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

El Bairi, K., Kandhro, A.H., Gouri, A. et al. Emerging diagnostic, prognostic and therapeutic biomarkers for ovarian cancer. Cell Oncol. 40, 105–118 (2017). https://doi.org/10.1007/s13402-016-0309-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13402-016-0309-1

Keywords

Search

Navigation