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  • Huttenhain, RuthETH Zürich (author)

A targeted mass spectrometry strategy for developing proteomic biomarkers : a case study of epithelial ovarian cancer

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:275edae5-a731-4812-a394-5d008a254701
  • https://lup.lub.lu.se/record/275edae5-a731-4812-a394-5d008a254701URI
  • https://doi.org/10.1074/mcp.RA118.001221DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Protein biomarkers for epithelial ovarian cancer are critical for the early detection of the cancer to improve patient prognosis and for the clinical management of the disease to monitor treatment response and to detect recurrences. Unfortunately, the discovery of protein biomarkers is hampered by the limited availability of reliable and sensitive assays needed for the reproducible quantification of proteins in complex biological matrices such as blood plasma. In recent years, targeted mass spectrometry, exemplified by Selected Reaction Monitoring (SRM) has emerged as a method, capable of overcoming this limitation. Here, we present a comprehensive SRM-based strategy for developing plasma-based protein biomarkers for epithelial ovarian cancer and illustrate how the SRM platform, when combined with rigorous experimental design and statistical analysis, can result in detection of predictive analytes.Our biomarker development strategy first involved a discovery-driven proteomic effort to derive potential N-glycoprotein biomarker candidates for plasma-based detection of human ovarian cancer from a genetically engineered mouse model of endometrioid ovarian cancer, which accurately recapitulates the human disease. Next, 65 candidate markers selected from proteins of different abundance in the discovery dataset were reproducibly quantified with SRM assays across a large cohort of over 200 plasma samples from ovarian cancer patients and healthy controls. Finally, these measurements were used to derive a 5-protein signature for distinguishing individuals with epithelial ovarian cancer from healthy controls. The sensitivity of the candidate biomarker signature in combination with CA125 ELISA-based measurements currently used in clinic, exceeded that of CA125 ELISA-based measurements alone. The SRM-based strategy in this study is broadly applicable. It can be used in any study that requires accurate and reproducible quantification of selected proteins in a high-throughput and multiplexed fashion.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Choi, MeenaNortheastern University (author)
  • Martin de la Fuente, LauraLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Bröst- och ovarialcancer,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Breast and Ovarian Cancer Genomics,Lund University Research Groups(Swepub:lu)med-lrm (author)
  • Oehl, KathrinUniversity Hospital of Zurich (author)
  • Chang, Ching-YunPurdue University (author)
  • Zimmermann, Anne-KathrinUniversity Hospital of Zurich (author)
  • Malander, SusanneLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-sma (author)
  • Olsson, HakanLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund Melanoma Study Group,Lund University Research Groups(Swepub:lu)onk-hol (author)
  • Surinova, SilviaETH Zürich (author)
  • Clough, TimothyPurdue University (author)
  • Heinzelmann-Schwarz, ViolaUniversity Hospital Basel (author)
  • Wild, Peter JUniversity Hospital Frankfurt (author)
  • Dinulescu, DanielaHarvard Medical School (author)
  • Niméus, EmmaLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Bröstcancerkirurgi,Forskargrupper vid Lunds universitet,Bröstcancer Proteogenomik,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Breast Cancer Surgery,Lund University Research Groups,Breast cancer Proteogenomics(Swepub:lu)onk-ens (author)
  • Vitek, OlgaNortheastern University (author)
  • Aebersold, RuediETH Zürich (author)
  • ETH ZürichNortheastern University (creator_code:org_t)

Related titles

  • In:Molecular and Cellular Proteomics18:9, s. 1836-18501535-9484

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