Metabolic Profiles Of Plasma Samples From Patients With Colorectal Cancer, Colorectal Adenomas, And Controls
David HUGHES, Royal College of Surgeons in Ireland, Ireland
HUGHES D. 1
, DUARTE-SALLES T. 2
, ACHAINTRE D. 3
, NEARY P. 4
, VODICKA P. 5,6
, MIROSLAV L. 6
, JENAB M. 7
, SCALBERT A. 3
1 Department of Physiology & Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin 2, Ireland
2 Institut Universitari dInvestigaciķ en Atenciķ Primāria Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain
3 Section of Nutrition and Metabolism, Biomarkers Group, International Agency for Research on Cancer, Lyon, France
4 Department of Colorectal Surgery, AMNCH Hospital, Dublin 24, Ireland
5 Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic
6 1st Medical Faculty of Charles University & Thomayer University Hospital, Prague, Czech Republic
7 Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France
Purpose: Metabolomics is a promising high-throughput approach to define metabolic biomarkers associated with cancer and to help provide insight into the role of metabolism in carcinogenesis or responses to disease treatment. The primary objective of this colorectal cancer (CRC) patient study is to locate plasma metabolic biomarkers distinguishing three patient groups (cancers, adenomas, and disease-free) to inform CRC screening strategies. Secondary objectives are to: (1) Associate a metabolic profile with colorectal neoplasia pathology or location, and (2) Examine the metabolic profile of the cancers with regard to clinical outcome (i.e., do particular metabolic profiles associate with disease prognosis or treatment response?).
Methods: One hundred forty five metabolites were measured in 390 plasma samples from sample cohorts from Ireland and the Czech Republic using the AbsoluteIDQ® p180 kit (Biocrates, Innsbruck, Austria) and a Q-trap 5500 mass-spectrometer (AB-Sciex, Framingham, MA). The Irish study includes 27 CRC patients, 133 with advanced adenomas or polyps, and 57 controls (normal after colonoscopy). The Czech group comprises 126 CRC patients and 47 blood-donor controls of a similar age range. The different concentrations and ratios of metabolites will be analysed as continuous and categorical variables. Correlations of metabolite levels will be represented by heat maps among cases (CRC or adenoma) and controls, and differences in levels between cases and controls will be estimated by t-tests and ANOVA. Logistic regression models will be used to estimates odds ratios for significant difference between disease state. Differences by batch, cancer stage, treatment responses and survival outcomes, sex, country, cases and controls will also be assessed.
Results & Conclusions: As we are still finishing the final sample runs and analysing our results, the findings will be presented at the meeting.
Funding: Sample collections were funded by AZV 15-27580A (Czech Ministry of Health) and the Meath Foundation grant 2008-2010 (Dublin, Ireland).