Affiliations: Department of Surgical Gastroenterology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
Correspondence:
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Corresponding author: Louise Rasmussen, Department of Surgical Gastroenterology, Hvidovre Hospital, University of Copenhagen, Kettegaard Alle 30, Hvidovre, 2650, Denmark. Tel.: +45 38620637; E-mail: [email protected].
Note: [1] Deceased.
Abstract: BACKGROUND: Blood-based protein biomarkers for detection of colorectal cancer (CRC) have been submitted to intense research to improve the full potential in screening for CRC. OBJECTIVE: The aim was to explore the diagnostic performance of 92 proteins related to inflammation and carcinogenesis in detection of CRC or precancerous lesions. METHODS: Blood-samples were collected from 4,698 individuals undergoing colonoscopy. An explorative unmatched case-control study was designed with 294 cases (individuals with CRC or high-risk colorectal adenoma) and 490 controls (individuals with low-risk colorectal adenoma, non-malignant findings or clean colorectum at colonoscopy). Protein profiling was performed by multiplex proximity extension assay. Statistical analyses were performed as univariate and multivariate logistic regression analyses. RESULTS: Univariably, CSF-1, MMP12 and IL8 demonstrated superior performance in discrimination of individuals with CRC. Recurrently, IL8 was included as contributor in majority of multivariate models discriminating individuals with CRC. The multivariate evaluation in discrimination of individuals with CRC demonstrated AUC=ROC 0.82, sensitivity = 0.39 at specificity = 0.80. Discrimination of individuals with late stage CRC from individuals with clean colorectum demonstrated AUC=ROC 0.90, sensitivity = 0.58 at specificity = 0.80. CONCLUSIONS: A subset of biomarker candidates, specifically IL8, investigated in the present study suggest a potential as blood-based biomarkers in screening of CRC.
Keywords: Protein biomarker, IL8, colorectal neoplasia, proximity extension assay, early detection of cancer, inflammation, carcinogenesis
