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. 2016 Jan 15;6(2):321-30.
eCollection 2016.

Hydroxylated collagen peptide in urine as biomarker for detecting colorectal liver metastases

Zarina S Lalmahomed  1 , Mirelle Ee Bröker  1 , Nick A van Huizen  2 , Robert R J Coebergh van den Braak  1 , Lennard Jm Dekker  3 , Dimitris Rizopoulos  4 , Cornelis Verhoef  5 , Ewout W Steyerberg  6 , Theo M Luider  3 , Jan Nm IJzermans  1
Affiliations

Hydroxylated collagen peptide in urine as biomarker for detecting colorectal liver metastases

Zarina S Lalmahomed et al. Am J Cancer Res. .

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.

Keywords: Colorectal liver metastases; biomarker; collagen; mass spectrometry; urine.

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Figures

Figure 1
Figure 1
The hydroxylation pattern of AGP was confirmed by MS2. The high resolution spectra of endogenous (top) and stable isotope-labeled peptides (bottom) were compared and found to be identical.
Figure 2
Figure 2
A and B. Distribution of data points based on a) the urine AGP ratios and b) serum CEA levels. AGP cut-off = 1.223, CEA cut-off = 5 µg/L. HKD = healthy kidney donors; RFC = relapse-free controls; PCC = primary colorectal cancer controls.
Figure 3
Figure 3
Distribution of data points based on the final multivariate regression analysis combining serum CEA and urine AGP levels. HKD = healthy kidney donors; RFC = relapse-free controls; PCC = primary colorectal cancer controls.
See this image and copyright information in PMC

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