Targeted metabolomics in colorectal cancer: a strategic approach using standardized laboratory tests of the blood and urine

• Main Authors: Jerzak KJ, Laureano M, Elsharawi R, Kavsak P, Chan KKW, Dhesy-Thind SK, Zbuk K
• Format: Article
• Language: English
• Published: Dove Medical Press 2017-05-01
• Series: Hypoxia
• Subjects: Metabolism; metabolomics; biomarker; colorectal cancer; hypoxia; venous CO2
• Online Access: https://www.dovepress.com/targeted-metabolomics-in-colorectal-cancer-a-strategic-approach-using--peer-reviewed-article-HP

Katarzyna J Jerzak,1,2 Marissa Laureano,3 Radwa Elsharawi,4 Peter Kavsak,5 Kelvin KW Chan,2,6 Sukhbinder K Dhesy-Thind,7 Kevin Zbuk7 1Department of Medicine, University of Toronto, Toronto, Ontario, 2Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, 3Department of Medicine, McMaster University, Hamilton, Ontario, 4Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, 5Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, 6Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, 7Department of Oncology, McMaster University, Hamilton, Ontario, Canada Background: Glycolytic markers have been detected in colorectal cancer (CRC) using advanced analytical methods. Methods: Using commercially available assays, by-products of anaerobic metabolism were prospectively measured in the blood and urine of 20 patients with metastatic colorectal cancer (mCRC) and 20 patients with local disease. Twenty-four-hour urine citrate, plasma lactate, ketones, venous blood gas, anion gap, and osmolar gap were investigated. Results of patients with metastatic and local CRC were compared using two-sample t-tests or equivalent nonparametric tests. In addition, plasma total CO2 concentrations in our local hospital (5,931 inpatients and 1,783 outpatients) were compared retrospectively with those in our dedicated cancer center (1,825 outpatients) over 1 year. Results: The average venous pCO2 was higher in patients with mCRC (50.2 mmHg; standard deviation [SD]=9.36) compared with those with local disease (42.8 mmHg; SD=8.98), p=0.045. Calculated serum osmolarity was higher in mCRC and attributed to concomitant sodium and urea elevations. In our retrospective analysis, plasma total CO2 concentrations (median=27 mmol/L) were higher in cancer patients compared to both hospital inpatients (median=23 mmol/L) and outpatients (median=24 mmol/L), p<0.0001. Conclusion: Patients with mCRC had higher venous pCO2 levels than those with local disease. Although causation cannot be established, we hypothesize that pCO2 elevation may stem from a perturbed metabolism in mCRC. Keywords: metabolism, metabolomics, biomarker, colorectal cancer, hypoxia, venous CO2