Abstract 1154: Serum and urine markers of metabolic dysfunction in colorectal cancer: A pilot study
Authors: Jerzak Katarzyna Joanna , Laureano Marissa , Kavsak Peter A. , Dhesy-Thind Sukhbinder , Zbuk Kevin 
Published: August 2015

Objective: Intra-tumor hypoxia portends a poor prognosis and may result in resistance to chemotherapy and radiotherapy, but systemic markers of hypoxia have not been investigated. In this study, by-products of anaerobic metabolism were measured in the serum and urine of patients with metastatic colorectal cancer (CRC) and compared to patients with local disease.

Material and methods: In this prospective pilot study, 42 patients with biopsy-proven colorectal adenocarcinoma (21 with metastatic and 21 with local disease) were recruited at St. Joseph's Hospital and the Juravinski Hospital and Cancer Centre in Hamilton, ON, Canada. Exclusion criteria included resection of the primary tumor, metastectomy, insulin-dependent diabetes, chemotherapy or radiation therapy within 2 weeks, infection requiring antibiotics, hospitalization within 2 weeks and creatinine clearance &lt;30 mL/min. 24 hour urine citrate, plasma lactate, serum ketones, venous blood gas (VBG), serum bicarbonate and indirect markers of small molecules, both charged (anion gap) and un-charged (osmolar gap) were investigated. Results of patients with metastatic CRC were compared to i) results of the local CRC cohort, and ii) reference values using t-tests.

Results: The average age of study participants was 67±13 years. All patients had active cancer at the time of their study investigations; those with metastatic were on a drug holiday for a time period that ranged from 2 weeks to 12 months. None of the included patients were diagnosed with de-novo metastatic disease. The average pCO2 (50±3 mmHg) and calculated serum osmolality (299±3 mmol/kg) border the upper limit of normal among patients with metastatic CRC. Further, the average pCO2 (50±3 vs. 45±4 mmHg, p = 0.05), calculated serum osmolality (299±3 vs. 292±3 mmol/kg, p = 0.01), and serum bicarbonate (28±1 vs. 26±1 mmol/L, p = 0.03) were statistically higher among patients with metastatic CRC as compared to those with local disease. Serum ketones were negative in all patients. Measured serum osmolality, osmolar gap, lactate, anion gap, pH and 24 hour urine citrate did not vary significantly between the two groups.

Conclusions: In our pilot study, pCO2 and serum bicarbonate levels were statistically higher among patients with metastatic colorectal cancer (n = 21) as compared to those with local disease (n = 21). We hypothesize that higher levels of pCO2 are observed in patients with metastatic colorectal cancer due to a higher burden of disease and a greater extent of glycolysis. Higher bicarbonate levels, which were concurrently observed, are likely a result of physiological compensation for elevated pCO2 in order to maintain a normal pH. Serum pCO2 and bicarbonate may have the potential to serve as novel biomarkers in colorectal cancer and other tumors that are known to be hypoxic. Future studies to assess their correlation with intra-tumor hypoxia or clinical prognosis are warranted.

Citation Format: Katarzyna Joanna Jerzak, Marissa Laureano, Peter A. Kavsak, Sukhbinder Dhesy-Thind, Kevin Zbuk. Serum and urine markers of metabolic dysfunction in colorectal cancer: A pilot study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1154. doi:10.1158/1538-7445.AM2015-1154