Ovarian Cancer Biomarkers: Moving Forward in Early Detection

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1219)


Ovarian cancer is a silent cancer which rate survival mainly relays in early stage detection. The discovery of reliable ovarian cancer biomarkers plays a crucial role in the disease management and strongly impact in patient’s prognosis and survival. Although having many limitations CA125 is a classical ovarian cancer biomarker, but current research using proteomic or metabolomic methodologies struggles to find alternative biomarkers, using non-invasive our relatively non-invasive sources such as urine, serum, plasma, tissue, ascites or exosomes. Metabolism and metabolites are key players in cancer biology and its importance in biomarkers discovery cannot be neglected. In this chapter we overview the state of art and the challenges facing the use and discovery of biomarkers and focus on ovarian cancer early detection.


Cancer biomarkers Ovarian cancer Early detection Urine biomarkers Proteomics Metabolomics 



Apolipoprotein A-1


Advanced Stage


Cancer Antigen 125


Collagen alpha-1 (III)


Elastin microfibril interfacer 2


Ephrin receptor A8


Early Stage Disease


Food and Drug Administration


Fibrinogen alpha


Fibrinogen beta NT


Follicle-Stimulating Hormone


Ferritin light chain


Human Epididymis protein 4




Heat Shock Protein 27


Insulin-like Growth Factor 2


Interleukin-2 Receptor α


Inter-α-Trypsin Inhibitor heavy chain H4


N-acetyl-D-glucosamine kinase


Nucleoside diphosphate kinase A


Reg-alpha fragment


Phosphatidylethanolamine Binding Protein 1


Protein phosphatase-1


Peroxiredoxin II


Proteasome alpha-6


Mitochondrial short-chain enoyl-CoA hydratase




Transvaginal Ultrasonography


von Willebrand factor


  1. Ahmed N, Barker G, Oliva KT, Hoffmann P, Riley C, Reeve S, Smith AI, Kemp BE, Quinn MA, Rice GE (2004) Proteomic-based identification of haptoglobin-1 precursor as a novel circulating biomarker of ovarian cancer. Br J Cancer 91:129–140PubMedPubMedCentralCrossRefGoogle Scholar
  2. Ahmed N, Oliva KT, Barker G, Hoffmann P, Reeve S, Smith IA, Quinn MA, Rice GE (2005) Proteomic tracking of serum protein isoforms as screening biomarkers of ovarian cancer. Proteomics 5:4625–4636PubMedCrossRefPubMedCentralGoogle Scholar
  3. Akinyemiju T, Moore JX, Judd SE, Pisu M, Goodman M, Howard VJ, Long L, Safford M, Gilchrist SC, Cushman M (2018) Pre-diagnostic biomarkers of metabolic dysregulation and cancer mortality. Oncotarget 9:16099–16109PubMedPubMedCentralCrossRefGoogle Scholar
  4. An HJ, Kim DS, Park YK, Kim SK, Choi YP, Kang S, Ding B, Cho NH (2006) Comparative proteomics of ovarian epithelial tumors. J Proteome Res 5:1082–1090PubMedCrossRefPubMedCentralGoogle Scholar
  5. Anderson NL, Anderson NG (2002) The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics 1:845–867PubMedPubMedCentralCrossRefGoogle Scholar
  6. Anderson NS, Bermudez Y, Badgwell D, Chen R, Nicosia SV, Bast RC Jr, Kruk PA (2009) Urinary levels of Bcl-2 are elevated in ovarian cancer patients. Gynecol Oncol 112(1):60–67PubMedCrossRefPubMedCentralGoogle Scholar
  7. Badgwell D, Lu Z, Cole L, Fritsche H, Atkinson EN, Somers E, Allard J, Moore RG, Lu KH, Bast RC Jr (2007) Urinary mesothelin provides greater sensitivity for early stage ovarian cancer than serum mesothelin, urinary hCG free beta subunit and urinary hCG beta core fragment. Gynecol Oncol 106(3):490–497PubMedPubMedCentralCrossRefGoogle Scholar
  8. Bast RC Jr, Xu FJ, Yu YH, Barnhill S, Zhang Z, Mills GB (1998) CA125: the past and the future. Int J Biol Markers 13:179–187PubMedCrossRefPubMedCentralGoogle Scholar
  9. Bergen HR 3rd, Vasmatzis G, Cliby WA, Johnson KL, Oberg AL, Muddiman DC (2003) Discovery of ovarian cancer biomarkers in serum using NanoLC electrospray ionization TOF and FT-ICR mass spectrometry. Dis Markers 19:239–249PubMedCrossRefPubMedCentralGoogle Scholar
  10. Bharti SK, Wildes F, Hung CF, Wu TC, Bhujwalla ZM, Penet MF (2017) Metabolomic characterization of experimental ovarian cancer ascitic fluid. Metabolomics 13:113PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bosco C, Wulaningsih W, Melvin J, Santaolalla A, De Piano M, Arthur R, Van Hemelrijck M (2015) Metabolic serum biomarkers for the prediction of cancer: a follow-up of the studies conducted in the Swedish AMORIS study. ecancer 9:555CrossRefGoogle Scholar
  12. Bruntz RC, Belshoff AC, Zhang Y, Macedo JKA, Higashi RM, Lane AN, Fan TW (2019) Inhibition of anaplerotic glutaminolysis underlies selenite toxicity in human lung cancer. Proteomics 12:e1800486CrossRefGoogle Scholar
  13. Chambers AF, Vanderhyden BC (2006) Ovarian cancer biomarkers in urine. Clin Cancer Res 12(2):323–327PubMedCrossRefPubMedCentralGoogle Scholar
  14. Cohen JG, White M, Cruz A, Farias-Eisner R (2014) In 2014, can we do better than CA125 in the early detection of ovarian cancer? World J Biol Chem 5(3):286–300PubMedPubMedCentralCrossRefGoogle Scholar
  15. Coleman R, Herzog T, Chan D, Munroe D, Pappas T, Smith A, Zhang Z, Wolf J (2016) Validation of a second-generation multivariate index assay for malignancy risk of adnexal masses. Am J Obstet Gynecol 215:82.e1–82.e11CrossRefGoogle Scholar
  16. Collins RRJ, Patel K, Putnam WC, Kapur P, Rakheja D (2017) Oncometabolites: a new paradigm for oncology, metabolism, and the clinical laboratory. Clin Chem 63(12):1812–1820PubMedCrossRefPubMedCentralGoogle Scholar
  17. Dando I, Pozza ID, Ambrosini G, Torrens-Mas M, Butera G, Mullappilly N, Pacchiana R, Palmieri M, Donadelli M (2019) Oncometabolites in cancer aggressiveness and tumour repopulation. Biol Rev 94(4).
  18. Diavatis S, Papanikolaou A (2016) Level of HE4 is correlated with diagnosis of struma ovarii: a case report. Am J Case Rep 17:459–461PubMedPubMedCentralCrossRefGoogle Scholar
  19. Drenberg CD, Saunders BO, Wilbanks GD, Chen R, Nicosia RF, Kruk PA, Nicosia SV (2010) Urinary angiostatin levels are elevated in patients with epithelial ovarian cancer. Gynecol Oncol 117(1):117–124PubMedCrossRefPubMedCentralGoogle Scholar
  20. Elzek MA, Rodland KD (2015) Proteomics of ovarian cancer: functional insights and clinical applications. Cancer Metastasis Rev 34:83–96PubMedPubMedCentralCrossRefGoogle Scholar
  21. Feng L, Dong Z, Tao D, Zhang Y, Liu Z (2018) The acidic tumor microenvironment: a target for smart cancer nano-theranostics. Natl Sci Rev 5(2):269–286CrossRefGoogle Scholar
  22. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, Forman D, Bray F (2013) Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49:1374–1403PubMedCrossRefPubMedCentralGoogle Scholar
  23. Fernandes C, Suares D, Yergeri MC (2018) Tumor microenvironment targeted nanotherapy. Front Pharmacol 9:1230PubMedPubMedCentralCrossRefGoogle Scholar
  24. Gobbo J, Marcion G, Cordonnier M, Dias AMM, Pernet N, Hammann A, Richaud S, Mjahed H, Isambert N, Clausse V, Rébé C, Bertaut A, Goussot V, Lirussi F, Ghiringhelli F, de Thonel A, Fumoleau P, Seigneuric R, Garrido C (2016) Restoring anticancer immune response by targeting tumor-derived exosomes with a HSP70 peptide aptamer. J Natl Cancer Inst 108(3).:djv330CrossRefGoogle Scholar
  25. Goo YA, Goodlett DR (2010) Advances in proteomic prostate cancer biomarker discovery. J Proteome 73:1839–1850CrossRefGoogle Scholar
  26. Grayson K, Gregory E, Khan G, Guinn B-A (2019) Urine biomarkers for the early detection of ovarian cancer – are we there yet? Biomark Cancer 11:1179299X19830977Google Scholar
  27. Gschwantler-Kaulich D, Weingartshofer S, Rappaport-Fürhauser C, Zeillinger R, Pils D, Muhr D, Braicu EI, Kastner MT, Tan YY, Semmler L, Sehouli J, Singer CF (2017) Diagnostic markers for the detection of ovarian cancer in BRCA1 mutation carriers. PLoS One 12(12):e0189641PubMedPubMedCentralCrossRefGoogle Scholar
  28. Guo L, Zhou B, Liu Z, Xu Y, Lu H, Xia M, Guo E, Shan W, Chen G, Wang C (2016) Blockage of glutaminolysis enhances the sensitivity of ovarian cancer cells to PI3K/mTOR inhibition involvement of STAT3 signaling. Tumour Biol 37(8):11007–11015PubMedCrossRefPubMedCentralGoogle Scholar
  29. Helleman J, van der Vlies D, Jansen MP, Luider TM, van der Burg ME, Stoter G, Berns EM (2008) Serum proteomic patterns for ovarian cancer monitoring. Int J Gynecol Cancer 18:985–995PubMedCrossRefPubMedCentralGoogle Scholar
  30. Horiuchi A, Itoh K, Shimizu M, Nakai I, Yamazaki T, Kimura K, Suzuki A, Shiozawa I, Ueda N, Konishi I (2003) Towards understanding the natural history of ovarian carcinoma development: a clinicopathologic approach. Gynecol Oncol 88:309–317PubMedCrossRefPubMedCentralGoogle Scholar
  31. Huber V, Camisaschi C, Berzi A, Ferro S, Lugini L, Triulzi T, Tuccitto A, Tagliabue E, Castelli C, Rivoltini L (2017) Cancer acidity: an ultimate frontier of tumor immune escape and a novel target of immunomodulation. Semin Cancer Biol 43:74–89PubMedCrossRefPubMedCentralGoogle Scholar
  32. Hurteau JA, Woolas RP, Jacobs IJ, Oram DC, Kurman CC, Rubin LA, Nelson DL, Berchuck A, Bast RC Jr, Mills GB (1995) Soluble interleukin-2 receptor α is elevated in sera of patients with benign ovarian neoplasms and epithelial ovarian cancer. Cancer 76:1615–1620PubMedCrossRefPubMedCentralGoogle Scholar
  33. Jackson D, Craven RA, Hutson RC, Graze I, Lueth P, Tonge RP, Hartley JL, Nickson JA, Rayner SJ, Johnston C, Dieplinger B, Hubalek M, Wilkinson N, Perren TJ, Kehoe S, Hall GD, Daxenbichler G, Dieplinger H, Selby PJ, Banks RE (2007) Proteomic profiling identifies afamin as a potential biomarker for ovarian cancer. Clin Cancer Res 13:7370–7379PubMedCrossRefPubMedCentralGoogle Scholar
  34. Jiang T, Lin Y, Yin H, Wang S, Sun Q, Zhang P, Bi W (2015) Correlation analysis of urine metabolites and clinical staging in patients with ovarian cancer. Int J Clin Exp Med 8(10):18165–18171PubMedPubMedCentralGoogle Scholar
  35. Kim K, Aronov P, Zakharkin SO, Anderson D, Perroud B, Thompson IM, Weiss RH (2009) Urine metabolomics analysis for kidney cancer detection and biomarker discovery. Mol Cell Proteomics 8:558–570PubMedPubMedCentralCrossRefGoogle Scholar
  36. Kozak KR, Su F, Whitelegge JP, Faull K, Reddy S, Farias-Eisner R (2005) Characterization of serum biomarkers for detection of early stage ovarian cancer. Proteomics 5:4589–4596PubMedCrossRefPubMedCentralGoogle Scholar
  37. Krell D, Battistino FS, Benafif S, Ganegoda L, Hall M, Rustin GJS (2017) Audit of CA125 follow-up after first-line therapy for ovarian cancer. Int J Gynecol Cancer 27(6):1118–1122PubMedPubMedCentralCrossRefGoogle Scholar
  38. Kutova OM, Guryev EL, Sokolova EA, Alzeibak R, Balalaeva IV (2019) Cancers (Basel) 11(1):68CrossRefGoogle Scholar
  39. Lambe M, Wigertz A, Garmo H, Walldius G, Jungner I, Hammar N (2011) Impaired glucose metabolism and diabetes and the risk of breast, endometrial, and ovarian cancer. Cancer Causes Control 22(8):1163–1171PubMedCrossRefPubMedCentralGoogle Scholar
  40. Lemaire R, Menguellet SA, Stauber J, Marchaudon V, Lucot JP, Collinet P, Farine MO, Vinatier D, Day R, Ducoroy P, Salzet M, Fournier I (2007) Specific MALDI imaging and profiling for biomarker hunting and validation: fragment of the 11S proteasome activator complex, Reg alpha fragment, is a new potential ovary cancer biomarker. J Proteome Res 6:4127–4134PubMedCrossRefPubMedCentralGoogle Scholar
  41. Li XQ, Zhang SL, Cai Z, Zhou Y, Ye TM, Chiu JF (2009a) Proteomic identification of tumor-associated protein in ovarian serous cystadenocarcinoma. Cancer Lett 275:109–116PubMedCrossRefPubMedCentralGoogle Scholar
  42. Li J, Sherman-Baust CA, Tsai-Turton M, Bristow RE, Roden RB, Morin PJ (2009b) Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer. BMC Cancer 9:244PubMedPubMedCentralCrossRefGoogle Scholar
  43. Li J, Dowdy S, Tipton T, Podratz K, Lu WG, Xie X, Jiang SW (2009c) HE4 as a biomarker for ovarian and endometrial cancer management. Expert Rev Mol Diagn 9(6):555–566PubMedPubMedCentralCrossRefGoogle Scholar
  44. Lin J, Qin J, Li X, Dong P, Yin B (2012) Diagnostic value of human epididymis protein 4 compared with mesothelin for ovarian cancer: a systematic review and meta-analysis. Asian Pac. J Cancer Prev 13(11):5427–5432Google Scholar
  45. Liu X, Xu Y, Jin Q, Wang W, Zhang S, Wang X, Zhang Y, Xu X, Huang J (2016) EphA8 is a prognostic marker for epithelial ovarian cancer. Oncotarget 7(15):20801–20809PubMedPubMedCentralGoogle Scholar
  46. Lopes-Coelho F, Gouveia-Fernandes S, Gonçalves LG, Nunes C, Faustino I, Silva F, Félix A, Pereira SA, Serpa J (2016) HNF1β drives glutathione (GSH) synthesis underlying intrinsic carboplatin resistance of ovarian clear cell carcinoma (OCCC). Tumour Biol 37(4):4813–4829PubMedCrossRefPubMedCentralGoogle Scholar
  47. Melvin JC, Seth D, Holmberg L, Garmo H, Hammar N, Jungner I, Walldius G, Lambe M, Wigertz A, Van Hemelrijck M (2012) Lipid profiles and risk of breast and ovarian cancer in the Swedish AMORIS study. Cancer Epidemiol Biomark Prev 21(8):1381–1384CrossRefGoogle Scholar
  48. Mills GB, May C, McGill M, Roifman CM, Mellors A (1988) A putative new growth factor in ascitic fluid from ovarian cancer patients: identification, characterization, and mechanism of action. Cancer Res 48(5):1066–1071PubMedPubMedCentralGoogle Scholar
  49. Mok SC, Chao J, Skates S, Wong K, Yiu GK, Muto MG, Berkowitz RS, Cramer DW (2001) Prostasin, a potential serum marker for ovarian cancer: identification through microarray technology. J Natl Cancer Inst 93:1458–1464PubMedCrossRefPubMedCentralGoogle Scholar
  50. Mor G, Visintin I, Lai Y, Zhao H, Schwartz P, Rutherford T, Yue L, Bray-Ward P, Ward DC (2005) Serum protein markers for early detection of ovarian cancer. Proc Natl Acad Sci U S A 102:7677–7682PubMedPubMedCentralCrossRefGoogle Scholar
  51. Moshkovskii SA, Serebryakova MV, Kuteykin-Teplyakov KB, Tikhonova OV, Goufman EI, Zgoda VG, Taranets IN, Makarov OV, Archakov AI (2005) Ovarian cancer marker of 11.7 kDa detected by proteomics is a serum amyloid A1. Proteomics 5:3790–3797PubMedCrossRefPubMedCentralGoogle Scholar
  52. Moss EL, Hollingworth J, Reynolds TM (2005) The role of CA125 in clinical practice. J Clin Pathol 58:308–312PubMedPubMedCentralCrossRefGoogle Scholar
  53. Muthu M, Nordström A (2019) Current status and future prospects of clinically exploiting cancer-specific metabolism – why is tumor metabolism not more extensively translated into clinical targets and biomarkers? Int J Mol Sci 20(6):1385PubMedCentralCrossRefGoogle Scholar
  54. Nunes SC, Ramos C, Lopes-Coelho F, Sequeira CO, Silva F, Gouveia-Fernandes S, Rodrigues A, Guimarães A, Silveira M, Abreu S, Santo VE, Brito C, Félix A, Pereira SA, Serpa J (2018) Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicity. Sci Rep 8(1):9513PubMedPubMedCentralCrossRefGoogle Scholar
  55. Ogiwara H, Takahashi K, Sasaki M, Kuroda T, Yoshida H, Watanabe R, Maruyama A, Makinoshima H, Chiwaki F, Sasaki H, Kato T, Okamoto A, Kohno T (2019) Targeting the vulnerability of glutathione metabolism in ARID1A-deficient cancers. Cancer Cell 35(2):177–190.e8PubMedCrossRefPubMedCentralGoogle Scholar
  56. Patriotis C, Maruvada P, Srivastav S (2017) Molecular detection and diagnosis of Cancer. In: Colemann WB, Tsongalis GJ (eds) The molecular basis of human cancer, 2nd edn. Springer, New YorkGoogle Scholar
  57. Petri AL, Simonsen AH, Yip TT, Hogdall E, Fung ET, Lundvall L, Hogdall C (2009) Three new potential ovarian cancer biomarkers detected in human urine with equalizer bead technology. Acta Obstet Gynecol Scand 88:18–26PubMedCrossRefPubMedCentralGoogle Scholar
  58. Plewa S, Horała A, Dereziński P, Nowak-Markwitz E, Matysiak J, Kokot ZJ (2019) Wide spectrum targeted metabolomics identifies potential ovarian cancer biomarkers. Life Sci 222:235–244PubMedCrossRefPubMedCentralGoogle Scholar
  59. Radpour R, Forouharkhou F (2018) Single-cell analysis of tumors: creating new value for molecular biomarker discovery of cancer stem cells and tumor-infiltrating immune cells. World J Stem Cells 10(11):160–171PubMedPubMedCentralCrossRefGoogle Scholar
  60. Rei M, Gonçalves-Sousa N, Lança T, Thompson RG, Mensurado S, Balkwill FR, Kulbe H, Pennington DJ, Silva-Santos B (2014) Murine CD27(−) Vγ6(+) γδ T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages. Proc Natl Acad Sci U S A 111(34):E3562–E3570PubMedPubMedCentralCrossRefGoogle Scholar
  61. Russo F, Lastoria S, Svanera G, Capobianco G, de Chiara A, di Francia R, Squame E, de Martinis F, Pinto A (2007) Long-term follow-up study on the role of serum CA-125 as a prognostic factor in 221 newly diagnosed patients with Hodgkin’s lymphoma. Leukemia Lymphoma 48(4):723–730PubMedCrossRefPubMedCentralGoogle Scholar
  62. Scholler N, Urban (2007) CA125 in ovarian cancer. Biomark Med 1(4):513–523PubMedPubMedCentralCrossRefGoogle Scholar
  63. Scholler N, Gross JA, Garvik B, Wells L, Liu Y, Loch CM, Ramirez AB, McIntosh MW, Lampe PD, Urban N (2008) Use of cancer-specific yeast-secreted in vivo biotinylated recombinant antibodies for serum biomarker discovery. J Transl Med 6:41PubMedPubMedCentralCrossRefGoogle Scholar
  64. Shirodkar SP, Lokeshwar VB (2009) Potential new urinary markers in the early detection of bladder cancer. Curr Opin Urol 19:488–493PubMedPubMedCentralCrossRefGoogle Scholar
  65. Slupsky CM, Steed H, Wells TH, Dabbs K, Schepansky A, Capstick V, Faught W, Sawyer MB (2010) Urine metabolite analysis offers potential early diagnosis of ovarian and breast cancers. Clin Cancer Res 16(23):5835–5841PubMedCrossRefGoogle Scholar
  66. Sutphen R, Xu Y, Wilbanks GD, Fiorica J, Grendys EC Jr, LaPolla JP, Arango H, Hoffman MS, Martino M, Wakeley K, Griffin D, Blanco RW, Cantor AB, Xiao YJ, Krischer JP (2004) Lysophospholipids are potential biomarkers of ovarian cancer. Cancer Epidemiol Biomark Prev 13(7):1185–1191Google Scholar
  67. Tanasova M, Begoyan VV, Weselinski LJ (2018) Targeting sugar uptake and metabolism for cancer identification and therapy: an overview. Curr Top Med Chem 18:467–483PubMedCrossRefPubMedCentralGoogle Scholar
  68. Wang M-L, Huang O, Yang T-X (2009) IgE myeloma with elevated level of serum CA125. J Zhejiang Univ Sci B 10(7):559–562PubMedPubMedCentralCrossRefGoogle Scholar
  69. Wang J, Gao J, Yao H, Wu Z, Wang M, Qi J (2014) Diagnostic accuracy of serum HE4, CA125 and ROMA in patients with ovarian cancer: a meta-analysis. Tumour Biol 35(6):6127–6138PubMedCrossRefPubMedCentralGoogle Scholar
  70. Woolas RP, Xu FJ, Jacobs IJ, Yu YH, Daly L, Berchuck A, Soper JT, Clarke-Pearson DL, Oram DH, Bast RC Jr (1993) Elevation of multiple serum markers in patients with stage I ovarian cancer. J Natl Cancer Inst 85(21):1748–1751PubMedCrossRefPubMedCentralGoogle Scholar
  71. Yang LV (2017) Tumor microenvironment and metabolism. Int J Mol Sci 18(12):2729PubMedCentralCrossRefGoogle Scholar
  72. Yang L, Moss T, Mangala LS, Marini J, Zhao H, Wahlig S, Armaiz-Pena G, Jiang D, Achreja A, Win J, Roopaimoole R, Rodriguez-Aguayo C, Mercado-Uribe I, Lopez-Berestein G, Liu J, Tsukamoto T, Sood AK, Ram PT, Nagrath D (2014) Metabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer. Mol Syst Biol 10:728PubMedPubMedCentralCrossRefGoogle Scholar
  73. Yang C, Kim HS, Song G, Lim W (2019) The potential role of exosomes derived from ovarian cancer cells for diagnostic and therapeutic approaches. J Cell Physiol:1–11Google Scholar
  74. Ye B, Cramer DW, Skates SJ, Gygi SP, Pratomo V, Fu L, Horick NK, Licklider LJ, Schorge JO, Berkowitz RS, Mok SC (2003) Haptoglobin-alpha subunit as potential serum biomarker in ovarian cancer: identification and characterization using proteomic profiling and mass spectrometry. Clin Cancer Res 9:2904–2911PubMedPubMedCentralGoogle Scholar
  75. Ye B, Skates S, Mok SC, Horick NK, Rosenberg HF, Vitonis A, Edwards D, Sluss P, Han WK, Berkowitz RS, Cramer DW (2006) Proteomic-based discovery and characterization of glycosylated eosinophil-derived-neurotoxin and C-terminal osteopontin fragments for ovarian cancer in urine. Clin Cancer Res 12:432–441PubMedCrossRefPubMedCentralGoogle Scholar
  76. Zhang Z, Bast RC Jr, Yu Y, Li J, Sokoll LJ, Rai AJ, Rosenzweig JM, Cameron B, Wang YY, Meng XY, Berchuck A, Van Haaften-Day C, Hacker NF, de Bruijn HW, van der Zee AG, Jacobs IJ, Fung ET, Chan DW (2004) Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer. Cancer Res 64:5882–5890PubMedCrossRefPubMedCentralGoogle Scholar
  77. Zhang B, Barekati Z, Kohler C, Radpour R, Asadollahi R, Holzgreve W, Zhong XY (2010) Proteomics and biomarkers for ovarian cancer diagnosis. Ann Clin Lab Sci 40(3):218–225PubMedPubMedCentralGoogle Scholar
  78. Zhang B, Cai FF, Zhong XY (2011) An overview of biomarkers for the ovarian cancer diagnosis. Eur J Obstet Gyn R B 158(2):119–123CrossRefGoogle Scholar
  79. Zhang X, Liu Y, Kim YJ, Mac J, Zhuang R, Wang P (2017) Co-delivery of carboplatin and paclitaxel via cross-linked multilamellar liposomes for ovarian cancer treatment. RSC Adv 7:19685–19693PubMedPubMedCentralCrossRefGoogle Scholar
  80. Zhao S, Yumei M, Xianghua H (2015) Trefoil factor 1 elevates the malignant phenotype of mucinous ovarian cancer cell through Wnt/β-catenin signaling. Int J Clin Exp Pathol 8(9):10412–10419PubMedPubMedCentralGoogle Scholar

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.IBB – Institute for Bioengineering and Biosciences, Instituto Superior TécnicoUniversidade de LisboaLisbonPortugal

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