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Next Generation Plasma Proteomics Identifies High-Precision Biomarker Candidates for Ovarian Cancer
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- Gyllensten, Ulf B. (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Uppsala kliniska forskningscentrum (UCR),Medicinsk genetik och genomik
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- Hedlund-Lindberg, J. (author)
- Uppsala Univ, Biomed Ctr, Dept Immunol Genet & Pathol, SciLifeLab Uppsala, SE-75108 Uppsala, Sweden.
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- Svensson, Johanna (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Science for Life Laboratory, SciLifeLab
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- Manninen, Johanna (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinska vetenskaper
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- Öst, Torbjörn (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Science for Life Laboratory, SciLifeLab
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- Ramsell, Jon (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinska vetenskaper
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- Åslin, Matilda (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinska vetenskaper
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- Ivansson, Emma (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi
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- Lomnytska, Marta, PhD, 1979- (author)
- Uppsala universitet,Reproduktiv hälsa
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- Lycke, Maria (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology,Gothenburg Univ, Inst Clin Sci, Dept Obstet & Gynaecol, Sahlgrenska Acad, SE-41685 Gothenburg, Sweden.
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- Axelsson, Tomas (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Science for Life Laboratory, SciLifeLab
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- Liljedahl, Ulrika (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Science for Life Laboratory, SciLifeLab
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- Nordlund, Jessica (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab
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- Edqvist, Per-Henrik D (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Experimentell och klinisk onkologi
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- Sjöblom, Tobias (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Experimentell och klinisk onkologi,Klinisk och experimentell patologi
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- Uhlén, Mathias (author)
- KTH,Science for Life Laboratory, SciLifeLab,Sci Life Lab, SE-17165 Stockholm, Sweden.
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- Stålberg, Karin (author)
- Uppsala universitet,Reproduktiv hälsa
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- Sundfeldt, Karin, 1962 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology,Gothenburg Univ, Inst Clin Sci, Dept Obstet & Gynaecol, Sahlgrenska Acad, SE-41685 Gothenburg, Sweden.
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- Åberg, Mikael (author)
- Uppsala universitet,Koagulation och inflammationsvetenskap,Science for Life Laboratory, SciLifeLab,Klinisk kemi
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- Enroth, Stefan (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Gyllensten
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(creator_code:org_t)
- 2022-03-30
- 2022
- English.
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In: Cancers. - : MDPI AG. - 2072-6694. ; 14:7
- Related links:
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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https://gup.ub.gu.se...
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https://doi.org/10.3...
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https://urn.kb.se/re...
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https://urn.kb.se/re...
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Abstract
Subject headings
Close
- Simple Summary Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. The aim of our study was to broadly measure protein biomarkers to find tests for the early detection of ovarian cancer. We found that combinations of 4-7 protein biomarkers can provide highly accurate detection of early- and late-stage ovarian cancer compared to benign conditions. The performance of the tests was then validated in a second independent cohort. Background: Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. Methods: We employed the Explore PEA technology for high-precision analysis of 1463 plasma proteins and conducted a discovery and replication study using two clinical cohorts of previously untreated patients with benign or malignant ovarian tumours (N = 111 and N = 37). Results: The discovery analysis identified 32 proteins that had significantly higher levels in malignant cases as compared to benign diagnoses, and for 28 of these, the association was replicated in the second cohort. Multivariate modelling identified three highly accurate models based on 4 to 7 proteins each for separating benign tumours from early-stage and/or late-stage ovarian cancers, all with AUCs above 0.96 in the replication cohort. We also developed a model for separating the early-stage from the late-stage achieving an AUC of 0.81 in the replication cohort. These models were based on eleven proteins in total (ALPP, CXCL8, DPY30, IL6, IL12, KRT19, PAEP, TSPAN1, SIGLEC5, VTCN1, and WFDC2), notably without MUCIN-16. The majority of the associated proteins have been connected to ovarian cancer but not identified as potential biomarkers. Conclusions: The results show the ability of using high-precision proteomics for the identification of novel plasma protein biomarker candidates for the early detection of ovarian cancer.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Obstetrics, Gynaecology and Reproductive Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- ovarian cancer
- protein biomarkers
- early detection
- marker
- diagnosis
- paths
- ca125
- Oncology
- ovarian cancer
Publication and Content Type
- ref (subject category)
- art (subject category)
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Cancers
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To the university's database
- By the author/editor
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Gyllensten, Ulf ...
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Hedlund-Lindberg ...
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Svensson, Johann ...
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Manninen, Johann ...
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Öst, Torbjörn
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Ramsell, Jon
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show more...
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Åslin, Matilda
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Ivansson, Emma
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Lomnytska, Marta ...
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Lycke, Maria
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Axelsson, Tomas
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Liljedahl, Ulrik ...
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Nordlund, Jessic ...
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Edqvist, Per-Hen ...
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Sjöblom, Tobias
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Uhlén, Mathias
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Stålberg, Karin
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Sundfeldt, Karin ...
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Åberg, Mikael
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Enroth, Stefan
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Obstetrics Gynae ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Cancers
- By the university
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University of Gothenburg
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Royal Institute of Technology
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Uppsala University