title: Hydroxylated collagen peptide in urine as biomarker for detecting colorectal liver metastases.
abstract: The clinical efficacy of carcinoembryonic antigen (CEA) as a marker of colorectal liver metastasis is limited, motivating a search for new biomarkers. Recently, urine proteomic analysis revealed AGPP(-OH)GEAGKP(-OH)GEQGVP(-OH)GDLGAP(-OH)GP (AGP), a promising peptide for this application. This study aimed to determine whether combining urine AGP testing with serum CEA analyses improves the sensitivity of detecting colorectal liver metastases. Urine samples from 100 patients with CRLM were collected prospectively and compared to three control groups: healthy kidney donors, patients who were relapse-free for 24 months after curative CRLM surgery, and primary colorectal cancer patients. A stable isotope labeled peptide standard was used to quantify the abundance of AGP in urine samples by selective reaction monitoring. Combined testing of urine AGP levels and serum CEA levels revealed a significantly increased sensitivity compared to CEA alone (85% vs. 68%, P<0.001; specificity 84% and 91%, respectively). No correlation was found between CEA and AGP-positive test results within individual patients (r(2) = 0.08). Urine AGP testing was negative in the three control groups. These results indicate that collagen-derived urine AGP peptide with a specific hydroxylation pattern combined with serum CEA levels may significantly improve the detection of colorectal liver metastases in patients at risk.
authors.affiliation: Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, Erasmus MC Rotterdam, The Netherlands.
authors.forename: Zarina S
authors.initials: ZS
authors.lastname: Lalmahomed
authors.affiliation: Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, Erasmus MC Rotterdam, The Netherlands.
authors.forename: Mirelle Ee
authors.initials: ME
authors.lastname: Bröker
authors.affiliation: Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, Erasmus MCRotterdam, The Netherlands; Department of Neurology, Erasmus MCRotterdam, The Netherlands.
authors.forename: Nick A
authors.initials: NA
authors.lastname: van Huizen
authors.affiliation: Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, Erasmus MC Rotterdam, The Netherlands.
authors.forename: Robert R J
authors.initials: RR
authors.lastname: Coebergh van den Braak
authors.affiliation: Department of Neurology, Erasmus MC Rotterdam, The Netherlands.
authors.forename: Lennard Jm
authors.initials: LJ
authors.lastname: Dekker
authors.affiliation: Department of Biostatistics, Erasmus MC Rotterdam, The Netherlands.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Rizopoulos
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Erasmus MC Rotterdam, The Netherlands.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Verhoef
authors.affiliation: Department of Public Health, Erasmus MC Rotterdam, The Netherlands.
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.affiliation: Department of Neurology, Erasmus MC Rotterdam, The Netherlands.
authors.forename: Theo M
authors.initials: TM
authors.lastname: Luider
authors.affiliation: Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, Erasmus MC Rotterdam, The Netherlands.
authors.forename: Jan Nm
authors.initials: JN
authors.lastname: IJzermans
keywords: Colorectal liver metastases; biomarker; collagen; mass spectrometry; urine