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Early Detection and Recurrence of Colorectal Adenomas by Combination of Eight Cancer-Associated Biomarkers in Plasma

Authors Rasmussen L, Nielsen HJ, Christensen IJ

Received 27 February 2020

Accepted for publication 27 July 2020

Published 13 August 2020 Volume 2020:13 Pages 273—284


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Andreas M. Kaiser

Louise Rasmussen, Hans Jørgen Nielsen, Ib Jarle Christensen

Department of Surgical Gastroenterology 360, Hvidovre Hospital, University of Copenhagen, Hvidovre 2650, Denmark

Correspondence: Louise Rasmussen
Department of Surgical Gastroenterology 360, Hvidovre Hospital, University of Copenhagen, Hvidovre 2650, Denmark

Introduction: Plasma levels of eight combined proteins have shown value as biomarkers for detection of colorectal cancer (CRC). However, their value in identifying colorectal adenoma needs further evaluation. The aim was to evaluate the eight proteins (AFP, CA19-9, CEA, CyFra21-1, Ferritin, Galectin-3, hs-CRP and TIMP-1) in detection of high-risk adenoma (HRA) and in prediction of recurrence of adenoma. Furthermore, the discrimination between HRA and low-risk adenoma (LRA) or CRC lesions was evaluated.
Methods: The study included 4698 individuals undergoing diagnostic colonoscopy. Automated ELISA platforms were used in the determination of protein levels in samples collected just before colonoscopy.
Results: Univariably, five proteins (AFP, CEA, CyFra21-1, hs-CRP and TIMP-1), respectively, significantly discriminated individuals with HRA from individuals with non-malignant findings. Multivariably, the combination of CEA and hs-CRP improved performance; AUC= 0.63 (sensitivity=0.19 at specificity=0.90). CyFra21-1, Ferritin and TIMP-1 demonstrated significant discrimination between individuals with HRA and LRA in univariable analyses, respectively. Performance was improved in multivariable analysis; AUC=0.61 (sensitivity=0.13 at specificity=0.90). Discrimination between individuals with colorectal adenomas and healthy individuals was significant for CA19-9, CEA, hs-CRP and TIMP-1, respectively, in univariable analyses. Multivariable analysis improved performance; AUC=0.63 (sensitivity=0.17 at specificity=0.90). All proteins except AFP demonstrated significant discrimination between individuals with HRA and CRC. Combination of CEA, CyFra21-1, Ferritin, hs-CRP and TIMP-1 in multivariable analysis improved discrimination; AUC=0.78 (sensitivity=0.34 at specificity=0.90). Association between plasma levels of any of the eight proteins and recurrence of colorectal adenomas after endoscopic removal could not be demonstrated.
Discussion: The protein panel shows a promising potential in detection of colorectal adenomas in general, but specifically of HRA. However, improvements are needed for the panel to be valuable as a screening test. Finally, plasma levels of the eight proteins were not predictive of recurrence of colorectal adenomas.

Keywords: biomarkers, tumor, neoplasm recurrence, local, colorectal adenomas, colorectal neoplasms, alpha-feto protein, cancer antigen 19-9, carcino embryogenic antigen, cytokeratin fragment 21-1, Ferritin, Galectin-3, high sensitivity C-reactive protein, tissue inhibitor of metalloproteinases-1

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