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Circulating protein...
Circulating proteins reveal prior use of menopausal hormonal therapy and increased risk of breast cancer
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- Thomas, Cecilia Engel (author)
- KTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab
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- Dahl, Leo, 1995- (author)
- KTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab
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- Byström, Sanna (author)
- KTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab
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- Chen, Yan (author)
- Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A, SE-17177 Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden.
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- Uhlén, Mathias (author)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi
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- Mälarstig, Anders (author)
- Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A, SE-17177 Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden.
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- Czene, Kamila (author)
- Karolinska Institutet
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- Hall, Per (author)
- Karolinska Institutet
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- Schwenk, Jochen M. (author)
- KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik
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- Gabrielson, Marike (author)
- Karolinska Institutet
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(creator_code:org_t)
- Elsevier BV, 2022
- 2022
- English.
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In: Translational Oncology. - : Elsevier BV. - 1944-7124 .- 1936-5233. ; 17, s. 101339-
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Abstract
Subject headings
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- Accessible risk predictors are crucial for improving the early detection and prognosis of breast cancer. Blood samples are widely available and contain proteins that provide important information about human health and disease, however, little is still known about the contribution of circulating proteins to breast cancer risk prediction. We profiled EDTA plasma samples collected before diagnosis from the Swedish KARMA breast cancer cohort to evaluate circulating proteins as molecular predictors. A data-driven analysis strategy was applied to the molecular phenotypes built on 700 circulating proteins to identify and annotate clusters of women. The unsupervised analysis of 183 future breast cancer cases and 366 age-matched controls revealed five stable clusters with distinct proteomic plasma profiles. Among these women, those in the most stable cluster (N = 19; mean Jaccard index: 0.70 +/- 0.29) were significantly more likely to have used menopausal hormonal therapy (MHT), get a breast cancer diagnosis, and were older compared to the remaining clusters. The circulating proteins associated with this cluster (FDR < 0.001) represented physiological processes related to cell junctions (F11R, CLDN15, ITGAL), DNA repair (RBBP8), cell replication (TJP3), and included proteins found in female reproductive tissue (PTCH1, ZP4). Using a data-driven approach on plasma proteomics data revealed the potential long-lasting molecular effects of menopausal hormonal therapy (MHT) on the circulating proteome, even after women had ended their treatment. This provides valuable insights concerning proteomics efforts to identify molecular markers for breast cancer risk prediction.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Breast cancer
- Risk prediction
- Plasma proteomics
- Affinity proteomics
- Karma cohort
- Archetypal analysis
- Clustering
- Patient stratification
- Menopausal hormonal therapy
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Thomas, Cecilia ...
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Dahl, Leo, 1995-
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Byström, Sanna
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Chen, Yan
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Uhlén, Mathias
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Mälarstig, Ander ...
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show more...
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Czene, Kamila
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Hall, Per
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Schwenk, Jochen ...
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Gabrielson, Mari ...
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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 Cancer and Oncol ...
- Articles in the publication
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Translational On ...
- By the university
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Royal Institute of Technology
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Karolinska Institutet