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. 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.

Harbs, JustinUmeå universitet,Onkologi,Umeå University(Swepub:umu)juha0033 (författare)
Myte, RobinUmeå universitet,Onkologi,Umeå University(Swepub:umu)romy0001 (författare)
Brunius, Carl,1974Chalmers tekniska högskola,Chalmers University of Technology,Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; Chalmers Mass Spectrometry Infrastructure, Chalmers University of Technology, Gothenburg, Sweden(Swepub:cth)carlbru (författare)
Gunter, MarcInternational Agency for Research on Cancer (IARC),Section of Nutrition and Metabolism, International Agency for Research On Cancer, World Health Organization, Lyon, France (författare)
Palmqvist, RichardUmeå universitet,Patologi,Umeå University(Swepub:umu)ripa0001 (författare)
Liu, XijiaUmeå universitet,Institutionen för matematik och matematisk statistik,Umeå University(Swepub:umu)xili0017 (författare)
van Guelpen, BethanyUmeå universitet,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Onkologi,Umeå University(Swepub:umu)beyvan99 (författare)
Umeå universitetOnkologi (creator_code:org_t)

Ingår i:Scientific Reports: Springer Science and Business Media LLC11:12045-23222045-2322

Av författaren/redakt...: Harlid, Sophia, ...; Harbs, Justin; Myte, Robin; Brunius, Carl, 1 ...; Gunter, Marc; Palmqvist, Richa ...; visa fler...; Liu, Xijia; van Guelpen, Bet ...; visa färre...

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