Abstract B73: Increased serum fatty acyl carnitine levels may indicate development of advanced colorectal adenoma

Abstracts: AACR Special Conference: Metabolism and Cancer; June 7-10, 2015; Bellevue, WA Introduction: Colorectal cancer is the third most common cancer worldwide. Early detection of colorectal cancer dramatically improves survival rates. Thus, identification of early indicators may greatly reduce morbidity and mortality associated with this malignant cancer. The aim of this study was to identify early indicators of advanced colorectal adenoma in prospectively collected serum. Methods: We used a nested case-control study design in the Polyp Prevention Trial (PPT). All participants had a recent history of colorectal adenoma at baseline and underwent a colonoscopy at baseline and 4 years thereafter. 103 participants with an advanced adenoma 4 years after baseline were matched with 103 participants who remained polyp and adenoma free. Serum metabolites were measured by liquid chromatography/mass spectroscopy +/- electrospray ionization and gas chromatography/mass spectroscopy in samples collected at baseline (T0) and at the end of year 3 (T3). Changes in serum metabolite levels were compared overall and stratified by metabolic pathways using paired t-tests (parametric and non-parametric). Results: A total of 454 known serum metabolites were measured; of these, 294 were above the limit of detection in ≥90% of samples. A total of 100 metabolites changed significantly in adenoma cases at p < 0.05 (13 down- and 87 up-regulated) and 51 metabolites changed in adenoma cases at q < 0.05 (7 down- and 44 up-regulated) The most affected metabolic pathways were: fibrinogen cleavage proteins (all 3 up-regulated at q < 0.05), fatty acyl carnitines (7 of 9 up-regulated at p < 0.05 and 4 of 9 up-regulated at q < 0.05), nucleotide sugars (6 of 9 up-regulated at p < 0.05 and 3 of 9 up-regulated at q < 0.05), and non-esterified long-chain unsaturated fatty acids (9 of 12 up-regulated at p < 0.05 and 4 of 12 up-regulated at q < 0.05). 24 metabolites differed in ΔT3-T0 between advanced adenoma cases and controls at p < 0.05. The metabolic pathway most affected was fatty acyl carnitines (9 of 9 up-regulated compared to controls at p < 0.10 and 5 of 9 up-regulated compared to controls at p < 0.05). Conclusions: Increased serum fatty acyl carnitine levels may serve as early indicators of the development of advanced colorectal adenoma. Citation Format: Thushanthi H. Perera, Gwen Murphy, Matthew R. Young, Nancy H. Colburn, Elaine Lanza, Amanda J. Cross, Gerd Bobe. Increased serum fatty acyl carnitine levels may indicate development of advanced colorectal adenoma. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr B73.