Abstract

Marcos Vinicius ARAUJO Denadai*, Carlos Augusto Rodrigues Veo, Sandra Morini Silva, M. Gordian Adam, Udo Muller, Simon Schafferer, Ismael D C G Da Silva, Isabella Alves Brunetti and Delcio Matos

ABSTRACT

Metabolomics is an emerging analytical tool that has allowed cancer research to elucidate specific biomarkers and helped improve clinical outcomes. The aim of the project was to identify metabolic conditions in patients with colorectal cancer. A targeted metabolomic approach with the Biocrates Absolute IDQ® p180 Kit was used to quantify metabolites of various biochemical classes. The samples comprised 85 human cancer tissue and 85 cancer-surrounding tissue samples from the same patients. Classes of amino acids, biogenic amines, acylcarnitines, glycerophospholipids, sphingolipids and monosaccharides were analyzed. The statistical analysis included data normalization and quality control, Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), univariate statistics with significance testing, and analysis of fold changes. The main biochemical pathways affected were also analyzed. Univariate statistical analysis by comparing tumor and tumor-surrounding tissue found a total of 118 significantly altered metabolites. Tumor tissue samples displayed severely altered metabolomic features, which affected different pathophysiological pathways ranging from energy to lipid metabolism. Metabolomic reprogramming, glutaminolysis, prominent Warburg Effect, and increased IDO activity, which all have been described for cancer cells, could be conclusively observed in this analysis. The importance of lipid alterations occurring in tumor cells were also confirmed with this study. In colorectal cancer, the tumor and tumor-surrounding tissue present distinct metabolomic states and dramatic metabolomic reprogramming. Especially the role of sphingomyelins and lysophosphatidylcholines (lysoPCs) as potential tissue biomarkers for colorectal cancer needs further investigation.