Abstract LB-072: Differential plasma proteome analysis in patients with colorectal cancer from Colombia
Authors: María Carolina Sanabria-Salas, Ruth Andrea Rodríguez-Castro, Martha Lucía Serrano-López, Gustavo Hernández-Suárez, Myriam Sánchez de Gómez, Adriana Umaña-Pérez
Journal: Cancer Research (2017)

Abstract Introduction: Colorectal cancer (CRC) is the fourth leading cause of cancer death in Colombia, where mortality rates are increasing. Current screening and diagnosis methods range from non-invasive and not very sensitive and specific, such as occult blood in feces, to highly sensitive and specific but invasive, such as colonoscopy plus biopsy. Furthermore, the carcinoembryonic antigen in plasma, used as patient monitoring and prognostic biomarker, have a low specificity for the disease. Therefore, there is a need to find minimally invasive and accessible biomarkers that have potential as tools for screening, diagnosis or prognosis of CRC with a high sensitivity and specificity. Objective: To explore differences of plasma proteomic profiles between CRC cases and controls from Colombia, and to propose potential biomarkers of the disease. Materials and methods: We applied a bottom-up shotgun proteomics method to explore the plasma proteome profile of 20 CRC cases and 6 controls from Colombia, using RPLC coupled with an ESI-Q-Exactive Orbitrap. Mass spectra were collected in data-dependent mode with one MS precursor scan followed by 15 MS/MS scans. Mass spectra were analysed with X! Tandem, using the Uniprot Human Reference. 469 proteins were selected in Scaffold software after applying a Peptide and Protein Prophet scores of &amp;gt; 99% and &amp;gt; 95%, respectively, with a minimum of 2 peptides. Differential expression analyses were performed with the R package DESeq2 on the spectral count data, which uses a negative binomial GLM fitting and Wald statistics. Results: Using the first two principal components that explained 25% and 16% of the variance, led to separate most of the cases and controls of the study. We did not find significant differences in the only cases analyses (rectum vs. colon; left vs right; invasive vs in situ) after adjusting for multiple tests. When comparing CRC cases with controls we found 14 proteins differentially expressed (FDR &amp;lt; 0.05). Three of these proteins have a fold change of ± 2; LV401 and CD14 were found overexpressed in CRC cases whilst FBLN1 was found overexpressed in controls. Moreover, both supervised and unsupervised cluster analysis confirmed their utility as predictors of the disease. Conclusions: We identified a profile of 14 differentially expressed proteins among CRC cases compared to controls from Colombia. All these proteins have previously been found to be associated with CRC, or other cancer types, since they play an important role in the regulation or structure of the extracellular matrix, in the inflammatory response, in lipid metabolism and in drug resistance. Three of these are strong candidates as disease prognostic biomarkers (LV401, CD14 and FBLN1) according to what has been reported in the literature. Additional validation studies are required in a larger sample, including patients with CRC at different stages of the disease, in order to adequately assess their clinical utility. Citation Format: María Carolina Sanabria-Salas, Ruth Andrea Rodríguez-Castro, Martha Lucía Serrano-López, Gustavo Hernández-Suárez, Myriam Sánchez de Gómez, Adriana Umaña-Pérez. Differential plasma proteome analysis in patients with colorectal cancer from Colombia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-072. doi:10.1158/1538-7445.AM2017-LB-072