A two-tiered targeted proteomics approach to identify pre-diagnostic biomarkers of colorectal cancer risk
Colorectal cancer prognosis is dependent on stage, and measures to improve early detection are urgently needed. Using prospectively collected plasma samples from the population-based Northern Sweden Health and Disease Study, we evaluated protein biomarkers in relation to colorectal cancer risk. Appl...
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Umeå universitet, Onkologi
2021
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ftumeauniv:oai:DiVA.org:umu-181726 2023-10-09T21:54:33+02:00 A two-tiered targeted proteomics approach to identify pre-diagnostic biomarkers of colorectal cancer risk Harlid, Sophia Harbs, Justin Myte, Robin Brunius, Carl Gunter, Marc J. Palmqvist, Richard Liu, Xijia van Guelpen, Bethany 2021 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-181726 https://doi.org/10.1038/s41598-021-83968-6 eng eng Umeå universitet, Onkologi Umeå universitet, Patologi Umeå universitet, Institutionen för matematik och matematisk statistik Umeå universitet, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM) Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; Chalmers Mass Spectrometry Infrastructure, Chalmers University of Technology, Gothenburg, Sweden Section of Nutrition and Metabolism, International Agency for Research On Cancer, World Health Organization, Lyon, France Springer Nature Scientific Reports, 2021, 11:1, orcid:0000-0001-8540-6891 orcid:0000-0002-2974-2003 orcid:0000-0002-9933-2843 orcid:0000-0002-9692-101X http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-181726 doi:10.1038/s41598-021-83968-6 ISI:000626139000041 Scopus 2-s2.0-85102182478 info:eu-repo/semantics/openAccess Cancer and Oncology Cancer och onkologi Article in journal info:eu-repo/semantics/article text 2021 ftumeauniv https://doi.org/10.1038/s41598-021-83968-6 2023-09-22T14:01:18Z Colorectal cancer prognosis is dependent on stage, and measures to improve early detection are urgently needed. Using prospectively collected plasma samples from the population-based Northern Sweden Health and Disease Study, we evaluated protein biomarkers in relation to colorectal cancer risk. Applying a two-tiered approach, we analyzed 160 proteins in matched sequential samples from 58 incident colorectal cancer case–control pairs. Twenty-one proteins selected from both this discovery phase and the literature were then analyzed in a validation set of 450 case–control pairs. Odds ratios were estimated by conditional logistic regression. LASSO regression and ROC analysis were used for multi-marker analyses. In the main validation analysis, no proteins retained statistical significance. However, exploratory subgroup analyses showed associations between FGF-21 and colon cancer risk (multivariable OR per 1 SD: 1.23 95% CI 1.03–1.47) as well as between PPY and rectal cancer risk (multivariable OR per 1 SD: 1.47 95% CI 1.12–1.92). Adding protein markers to basic risk predictive models increased performance modestly. Our results highlight the challenge of developing biomarkers that are effective in the asymptomatic, prediagnostic window of opportunity for early detection of colorectal cancer. Distinguishing between cancer subtypes may improve prediction accuracy. However, single biomarkers or small panels may not be sufficient for effective precision screening. Article in Journal/Newspaper Northern Sweden Umeå University: Publications (DiVA) Scientific Reports 11 1 |
institution |
Open Polar |
collection |
Umeå University: Publications (DiVA) |
op_collection_id |
ftumeauniv |
language |
English |
topic |
Cancer and Oncology Cancer och onkologi |
spellingShingle |
Cancer and Oncology Cancer och onkologi Harlid, Sophia Harbs, Justin Myte, Robin Brunius, Carl Gunter, Marc J. Palmqvist, Richard Liu, Xijia van Guelpen, Bethany A two-tiered targeted proteomics approach to identify pre-diagnostic biomarkers of colorectal cancer risk |
topic_facet |
Cancer and Oncology Cancer och onkologi |
description |
Colorectal cancer prognosis is dependent on stage, and measures to improve early detection are urgently needed. Using prospectively collected plasma samples from the population-based Northern Sweden Health and Disease Study, we evaluated protein biomarkers in relation to colorectal cancer risk. Applying a two-tiered approach, we analyzed 160 proteins in matched sequential samples from 58 incident colorectal cancer case–control pairs. Twenty-one proteins selected from both this discovery phase and the literature were then analyzed in a validation set of 450 case–control pairs. Odds ratios were estimated by conditional logistic regression. LASSO regression and ROC analysis were used for multi-marker analyses. In the main validation analysis, no proteins retained statistical significance. However, exploratory subgroup analyses showed associations between FGF-21 and colon cancer risk (multivariable OR per 1 SD: 1.23 95% CI 1.03–1.47) as well as between PPY and rectal cancer risk (multivariable OR per 1 SD: 1.47 95% CI 1.12–1.92). Adding protein markers to basic risk predictive models increased performance modestly. Our results highlight the challenge of developing biomarkers that are effective in the asymptomatic, prediagnostic window of opportunity for early detection of colorectal cancer. Distinguishing between cancer subtypes may improve prediction accuracy. However, single biomarkers or small panels may not be sufficient for effective precision screening. |
format |
Article in Journal/Newspaper |
author |
Harlid, Sophia Harbs, Justin Myte, Robin Brunius, Carl Gunter, Marc J. Palmqvist, Richard Liu, Xijia van Guelpen, Bethany |
author_facet |
Harlid, Sophia Harbs, Justin Myte, Robin Brunius, Carl Gunter, Marc J. Palmqvist, Richard Liu, Xijia van Guelpen, Bethany |
author_sort |
Harlid, Sophia |
title |
A two-tiered targeted proteomics approach to identify pre-diagnostic biomarkers of colorectal cancer risk |
title_short |
A two-tiered targeted proteomics approach to identify pre-diagnostic biomarkers of colorectal cancer risk |
title_full |
A two-tiered targeted proteomics approach to identify pre-diagnostic biomarkers of colorectal cancer risk |
title_fullStr |
A two-tiered targeted proteomics approach to identify pre-diagnostic biomarkers of colorectal cancer risk |
title_full_unstemmed |
A two-tiered targeted proteomics approach to identify pre-diagnostic biomarkers of colorectal cancer risk |
title_sort |
two-tiered targeted proteomics approach to identify pre-diagnostic biomarkers of colorectal cancer risk |
publisher |
Umeå universitet, Onkologi |
publishDate |
2021 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-181726 https://doi.org/10.1038/s41598-021-83968-6 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Scientific Reports, 2021, 11:1, orcid:0000-0001-8540-6891 orcid:0000-0002-2974-2003 orcid:0000-0002-9933-2843 orcid:0000-0002-9692-101X http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-181726 doi:10.1038/s41598-021-83968-6 ISI:000626139000041 Scopus 2-s2.0-85102182478 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1038/s41598-021-83968-6 |
container_title |
Scientific Reports |
container_volume |
11 |
container_issue |
1 |
_version_ |
1779318165797339136 |