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Cellular Oncology

, Volume 40, Issue 2, pp 105–118 | Cite as

Emerging diagnostic, prognostic and therapeutic biomarkers for ovarian cancer

  • Khalid El BairiEmail author
  • Abdul Hafeez Kandhro
  • Adel Gouri
  • Wafaa Mahfoud
  • Noureddine Louanjli
  • Brahim Saadani
  • Said Afqir
  • Mariam Amrani
Review

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.

Keywords

Ovarian cancer Biomarkers Diagnosis Prognosis Circulating tumor cells Epigenetics 

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

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Supplementary Figure 1 (DOCX 69 kb)
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Supplementary Figure 5 (DOCX 65 kb)
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Supplementary Table 1 (DOCX 12 kb)
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Supplementary Table 2 (DOCX 16 kb)
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Supplementary Table 3 (DOCX 13 kb)
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Supplementary Table 4 (DOCX 13 kb)

References

  1. 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)CrossRefGoogle Scholar
  2. 2.
    R.L. Siegel, K.D. Miller, A. Jemal, Cancer statistics, 2016. CA Cancer J. Clin. 66, 7–30 (2016)PubMedCrossRefGoogle Scholar
  3. 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. 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)PubMedCrossRefGoogle Scholar
  5. 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)PubMedCrossRefGoogle Scholar
  6. 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)PubMedCrossRefGoogle Scholar
  7. 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)PubMedCrossRefGoogle Scholar
  8. 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)PubMedCrossRefGoogle Scholar
  9. 9.
    http://www.gopubmed.com/web/gopubmed/. Accessed 30 August 2016
  10. 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)PubMedCrossRefGoogle Scholar
  11. 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)PubMedCrossRefGoogle Scholar
  12. 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)CrossRefGoogle Scholar
  13. 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)CrossRefGoogle Scholar
  14. 14.
    M.E. Maradeo, P. Cairns, Translational application of epigenetic alterations: ovarian cancer as a model. FEBS Lett. 585, 2112–2120 (2011)PubMedPubMedCentralCrossRefGoogle Scholar
  15. 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)PubMedCrossRefGoogle Scholar
  16. 16.
    B.V. Chakravarthi, S. Nepal, S. Varambally, Genomic and epigenomic alterations in cancer. Am. J. Pathol. 186, 1724–1735 (2016)PubMedCrossRefGoogle Scholar
  17. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  18. 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)PubMedCrossRefGoogle Scholar
  19. 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. 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)PubMedCrossRefGoogle Scholar
  21. 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)PubMedCrossRefGoogle Scholar
  22. 22.
    J. Prat, New insights into ovarian cancer pathology. Ann. Oncol. 23 (Suppl 10), 111–117 (2012)Google Scholar
  23. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    R.J. Kurman, I.M. Shih, The dualistic model of ovarian carcinogenesis: revisited, revised, and expanded. Am. J. Pathol. 186, 733–747 (2016)PubMedCrossRefGoogle Scholar
  25. 25.
    Cancer Genome Atlas Research Network, Integrated genomic analyses of ovarian carcinoma. Nature 474, 609–615 (2011)CrossRefGoogle Scholar
  26. 26.
    A. Bamias, S. Pignata, E. Pujade-Lauraine, Angiogenesis: a promising therapeutic target for ovarian cancer. Crit. Rev. Oncol. Hematol. 84, 314–326 (2012)PubMedCrossRefGoogle Scholar
  27. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  28. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  29. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    I. Romero, R.C. Bast Jr., Minireview: human ovarian cancer: biology, current management, and paths to personalizing therapy. Endocrinology 153, 1593–1602 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  31. 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)PubMedCrossRefGoogle Scholar
  32. 32.
    O. Caron, Oncogenetics in the management of ovarian cancer: state-of-the art. Gynecol. Obstet. Fertil. 43, 335–337 (2015)PubMedCrossRefGoogle Scholar
  33. 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)Google Scholar
  34. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    J. Prat, Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch. 460, 237–249 (2012)PubMedCrossRefGoogle Scholar
  36. 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 PubMedPubMedCentralGoogle Scholar
  37. 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)PubMedCrossRefGoogle Scholar
  38. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  39. 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)PubMedCrossRefGoogle Scholar
  40. 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)PubMedCrossRefGoogle Scholar
  41. 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)PubMedCrossRefGoogle Scholar
  42. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  43. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  44. 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)PubMedCrossRefGoogle Scholar
  45. 45.
    V.A. Moyer, Screening for ovarian cancer: US preventive services task force reaffirmation recommendation statement. Ann. Intern. Med. 157, 900–904 (2012)PubMedCrossRefGoogle Scholar
  46. 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)PubMedCrossRefGoogle Scholar
  47. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    B.M. Nolen, A.E. Lokshin, Biomarker testing for ovarian cancer: clinical utility of multiplex assays. Mol. Diagn. Ther. 17, 139–146 (2013)PubMedPubMedCentralCrossRefGoogle Scholar
  49. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  50. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  51. 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)PubMedCrossRefGoogle Scholar
  52. 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)CrossRefGoogle Scholar
  53. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  54. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  55. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  56. 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)CrossRefGoogle Scholar
  57. 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)PubMedCrossRefGoogle Scholar
  58. 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)CrossRefGoogle Scholar
  59. 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)CrossRefGoogle Scholar
  60. 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)CrossRefGoogle Scholar
  61. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  62. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  63. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  64. 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)PubMedCrossRefGoogle Scholar
  65. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  66. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  67. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  68. 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)PubMedPubMedCentralGoogle Scholar
  69. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  70. 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. 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)PubMedCrossRefGoogle Scholar
  72. 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)CrossRefGoogle Scholar
  73. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  74. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  75. 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)CrossRefGoogle Scholar
  76. 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)CrossRefGoogle Scholar
  77. 77.
    M.V. Liberti, J.W. Locasale, The Warburg effect: how does it benefit cancer cells? Trends Biochem. Sci. 41, 211–218 (2016)PubMedPubMedCentralCrossRefGoogle Scholar
  78. 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)PubMedCrossRefGoogle Scholar
  79. 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)PubMedCrossRefGoogle Scholar
  80. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  81. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  82. 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. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  84. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  85. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    C. Escrevente, S. Keller, P. Altevogt, J. Costa, Interaction and uptake of exosomes by ovarian cancer cells. BMC Cancer 11, 108 (2011)PubMedPubMedCentralCrossRefGoogle Scholar
  87. 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)PubMedCrossRefGoogle Scholar
  88. 88.
    A. Bobrie, M. Colombo, G. Raposo, C. Thery, Exosome secretion: molecular mechanisms and roles in immune responses. Traffic 12, 1659–1668 (2011)PubMedCrossRefGoogle Scholar
  89. 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)PubMedCrossRefGoogle Scholar
  90. 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)PubMedCrossRefGoogle Scholar
  91. 91.
    O. Vaksman, C. Tropé, B. Davidson, R. Reich, Exosome-derived miRNAs and ovarian carcinoma progression. Carcinogenesis 35, 2113–2120 (2014)PubMedCrossRefGoogle Scholar
  92. 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)PubMedCrossRefGoogle Scholar
  93. 93.
    D. Hanahan, R.A. Weinberg, Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011)PubMedCrossRefGoogle Scholar
  94. 94.
    R. Paduch, The role of lymphangiogenesis and angiogenesis in tumor metastasis. Cell. Oncol. 39, 397–410 (2016)Google Scholar
  95. 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)CrossRefGoogle Scholar
  96. 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 PubMedGoogle Scholar
  97. 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 PubMedGoogle Scholar
  98. 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)PubMedCrossRefGoogle Scholar
  99. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  100. 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)PubMedPubMedCentralGoogle Scholar
  101. 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)PubMedPubMedCentralGoogle Scholar
  102. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  103. 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)CrossRefGoogle Scholar
  104. 104.
    E. Lengyel, Ovarian cancer development and metastasis. Am. J. Pathol. 177, 1053–1064 (2010)PubMedPubMedCentralCrossRefGoogle Scholar
  105. 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)PubMedCrossRefGoogle Scholar
  106. 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)Google Scholar
  107. 107.
    R. Drake, A.W. Vogl, A.W.M. Mitchel, Gray's anatomy for students (Churchill Livingstone/Elsevier, Philadelphia, 2010)Google Scholar
  108. 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)PubMedCrossRefGoogle Scholar
  109. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  110. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    M.A. Dawson, T. Kouzarides, Cancer epigenetics: from mechanism to therapy. Cell 150, 12–27 (2012)PubMedCrossRefGoogle Scholar
  112. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    A. Ferraro, Altered primary chromatin structures and their implications in cancer development. Cell. Oncol. 39, 195–210 (2016)CrossRefGoogle Scholar
  114. 114.
    E. Heard, R.A. Martienssen, Transgenerational epigenetic inheritance: myths and mechanisms. Cell 157, 95–109 (2014)PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    W.L. Tam, R.A. Weinberg, The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat. Med. 19, 1438–1449 (2013)PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    J.S. You, P.A. Jones, Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell 22, 9–20 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  117. 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. 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)PubMedCrossRefGoogle Scholar
  119. 119.
    C. Marsit, B. Christensen, Epigenetic Alterations in Oncogenesis, ed. by Adam R. Karpf (Springer, Berlin Heidelberg New York) (2013), pp. 233–252Google Scholar
  120. 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.Google Scholar
  121. 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)CrossRefGoogle Scholar
  122. 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)PubMedCentralCrossRefGoogle Scholar
  123. 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)PubMedCrossRefGoogle Scholar
  124. 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 PubMedGoogle Scholar
  125. 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)PubMedCrossRefGoogle Scholar
  126. 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)CrossRefGoogle Scholar
  127. 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)PubMedCrossRefGoogle Scholar
  128. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  129. 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)CrossRefGoogle Scholar
  130. 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)PubMedCrossRefGoogle Scholar
  131. 131.
    A. DiazLuis, A. Bardelli, Liquid biopsies: genotyping circulating tumor DNA. J. Clin. Oncol. 32, 579–586 (2014)CrossRefGoogle Scholar
  132. 132.
    H. Holger, M. Esteller, DNA methylation profiling in the clinic: applications and challenges. Nat. Rev. Genet. 13, 679–692 (2012)CrossRefGoogle Scholar
  133. 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)PubMedCrossRefGoogle Scholar
  134. 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)PubMedGoogle Scholar
  135. 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)Google Scholar
  136. 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)CrossRefGoogle Scholar
  137. 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)CrossRefGoogle Scholar
  138. 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)CrossRefGoogle Scholar
  139. 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)CrossRefGoogle Scholar
  140. 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)CrossRefGoogle Scholar
  141. 141.
    M. Vitiello, A. Tuccoli, L. Poliseno, Long non-coding RNAs in cancer: implications for personalized therapy. Cell. Oncol. 38, 17–28 (2015)CrossRefGoogle Scholar
  142. 142.
    M.D. Jansson, A.H. Lund, MicroRNA and cancer. Mol. Oncol. 6, 590–610 (2012)PubMedCrossRefGoogle Scholar
  143. 143.
    M. Acunzo, G. Romano, D. Wernicke, C.M. Croce, MicroRNA and cancer–a brief overview. Adv. Biol. Regul. 57, 1–9 (2015)PubMedCrossRefGoogle Scholar
  144. 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)CrossRefGoogle Scholar
  145. 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)PubMedCrossRefGoogle Scholar
  146. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  147. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  148. 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)PubMedCrossRefGoogle Scholar
  149. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  150. 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)PubMedCrossRefGoogle Scholar
  151. 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)PubMedCrossRefGoogle Scholar
  152. 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)PubMedCrossRefGoogle Scholar
  153. 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)PubMedCrossRefGoogle Scholar
  154. 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)PubMedCrossRefGoogle Scholar
  155. 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)PubMedPubMedCentralCrossRefGoogle Scholar
  156. 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)PubMedGoogle Scholar
  157. 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)PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© International Society for Cellular Oncology 2016

Authors and Affiliations

  • Khalid El Bairi
    • 1
    • 2
    Email author
  • Abdul Hafeez Kandhro
    • 3
  • Adel Gouri
    • 4
  • Wafaa Mahfoud
    • 5
  • Noureddine Louanjli
    • 6
  • Brahim Saadani
    • 7
  • Said Afqir
    • 8
  • Mariam Amrani
    • 9
  1. 1.Faculty of Medicine and PharmacyOujdaMorocco
  2. 2.Independent Research Team in Cancer Biology and Bioactive CompoundsMohammed 1st UniversityOujdaMorocco
  3. 3.Department of BiochemistryHealthcare Molecular and Diagnostic LaboratoryHyderabadPakistan
  4. 4.Laboratory of Medical BiochemistryIbn Rochd University HospitalAnnabaAlgeria
  5. 5.Laboratory of Biology and Health, URAC-34, Faculty of Science Ben MsikUniversity Hassan II, MohammediaCasablancaMorocco
  6. 6.Labomac IVF Centers and Clinical Laboratory MedicineCasablancaMorocco
  7. 7.IVF center IRIFIVClinique des IrisCasablancaMorocco
  8. 8.Department of Medical OncologyMohamed 1st University HospitalOujdaMorocco
  9. 9.Equipe de Recherche ONCOGYMA, Faculty of Medicine, Pathology Department, National Institute of OncologyUniversité Mohamed VRabatMorocco

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