Abstract 1154: Serum and urine markers of metabolic dysfunction in colorectal cancer: A pilot study
Bibliographic record
Abstract
Abstract 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 <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
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".