Abstract 3023: Identifying colorectal cancer biomarkers using a targeted proteomics platform with extensive coverage

Abstract

Abstract Despite advances in treatment, colorectal cancer remains one of the leading causes of cancer-specific death. To decrease colorectal cancer mortality, better and more cost-efficient tools for risk prediction and early detection are needed. One area that has shown promise is using protein biomarkers, measured in blood, to detect individuals with early-stage disease or at increased risk. The primary aim of this study was therefore to identify novel protein biomarkers associated with colorectal cancer risk and the secondary aim was to validate protein biomarkers that had been described in previous studies. We included data and samples from 185 incident colorectal cancer cases and 185 controls (matched on age, sex, sampling date, and the number of freeze-thaw cycles) from the Northern Sweden Health and Disease Study (NSHDS). Samples were collected between six years and three months prior to the diagnosis date of each case and concentrations of 1536 individual proteins were measured in plasma samples using the Olink Explore 1536 platform (Olink Proteomics). Prior to statistical analyses, 249 proteins were excluded, either due to not passing quality control or having more than 50% of the concentrations below the limit of detection. In addition, we also excluded extreme outliers. Conditional logistic regression was used to estimate Odds Ratios (ORs) and 95% confidence intervals (95% CI) for the association between protein concentrations and colorectal cancer risk. Multivariable models were adjusted for predetermined colorectal cancer risk factors, including body mass index, alcohol consumption, physical activity, smoking status, and level of education. When considering p<0.005 as a cut-off, we identified 20 proteins that were associated with colorectal cancer risk. Our top hit was TFF3 (Trefoil Factor 3) which was positively associated with colorectal cancer at a high significance level (multivariable OR per SD: 1.84 95% CI: 1.38 - 2.45). TFF3 was significant in men (FDR<0.1), but not in women (pheterogeneity <0.05). In addition, several of the top 20 proteins such as AREG, MMP7, and CXCL16 have been linked to the diagnosis or prognosis of colorectal cancer in earlier studies. To conclude, we identified one novel protein biomarker, TFF3, strongly associated with colorectal cancer risk and validated several proteins previously linked to the diagnosis or prognosis of colorectal cancer. Citation Format: Justin Harbs, Matilda Rentoft, Xijia Liu, Beatrice S. Melin, Sophia Harlid, Bethany Van Guelpen. Identifying colorectal cancer biomarkers using a targeted proteomics platform with extensive coverage [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3023.