Abstract 4369: Plasma metabolomic biomarkers for an early detection of colorectal cancer

Abstract

Abstract The aim of this study was to identify a plasma metabolic pattern characteristic of colorectal cancer (CRC) which could be used to assess the effectiveness of CRC surgery procedures and, eventually, support an early detection on CRC recurrence. CRC survival and treatment depends on accurate staging. In the past few years, numerous efforts have been made to discover new non-invasive biomarkers of CRC to enhance current diagnosis and prognostic capabilities. The metabolome is the result of the interaction of different -omic levels (genomic, epigenomic, transcriptional, proteomic) and the set of external interventions. Metabolites are involved in almost every biochemical reaction in the human body and provide a direct meaningful readout of its dynamic biochemical status. Because of that, metabolomics is a highly relevant approach to explore individual phenotypes in systems biology of cancer. This study reports results obtained from the metabolomic analysis of plasma samples collected from 40 CRC patients (stages I-IV) and 20 healthy controls matched by for age and gender. Blood from 20 matched post-CRC surgery cases (stages I-III) was collected 1-2 years after surgery to evaluate the correlation of changes in the plasma metabolome with surgery effectiveness. Metabolomic and lipidomic analysis was carried out by reversed phase LC-MS. The sample set was split into train (CRC pre-surgery (n=30) and Control (n=15) and test (CRC pre-surgery (n=10), CRC post-surgery (n=20) and Control(n=5)) subsets. The train set was used to build a multivariate model to discriminate CRC pre-surgery and Control groups and the test set was exclusively used to evaluate its generalization performance. Results from this exploratory study showed a statistically significant difference between the metabolic profiles of samples collected pre-CRC surgery and those collected post-surgery and from healthy individuals. Among other metabolites, CRC metabolic profile was characterized by lower levels of tryptophan and several carnitines (propionyl-carnitine, methyl-butirylcarnitine) and isoleucyl-leucine. Finally, our results indicate that these metabolites are at similar level than healthy individuals in post-CRC surgery samples. This cohort included only 2 CRC patients with diagnosed recurrence and 18 recurrence-free patients (stages I-III) within 3-4 years clinical follow-up after surgery and so, more data is required for the estimation of the predictive value of this metabolomic approach for the assessment of the treatment efficiency or disease progression. Conclusions: Our pilot study has identified a pattern of plasma metabolites that correlates with the presence of colorectal tumor. Furthermore, our results indicate that at 1 year post-CRC surgery these metabolites are normalized. Further work is required to establish whether these metabolites could serve as novel disease biomarkers for a minimally invasive diagnosis and monitoring of CRC. Citation Format: Anna Brunet-Vega, Maria Elisa Quilez, Carles Pericay, Ismael Macias, Laia Vilà, Eva Martinez-Balibrea, Sergio Lario, Guillermo Quintás. Plasma metabolomic biomarkers for an early detection of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4369.