Multidisciplinary approach for the study of the lipid metabolism in colon cancer

Abstract

Colorectal cancer is a leading cause of cancer death worldwide, its late detection contributes for become one of the deadliest. Research team of Lipids in Human Pathology has proven a relationship among membrane lipids and tumorigenic processes in CRC. Thus, the importance of studying the impact of colorectal cancer in the lipid composition during the differentiation process of colonocytes. Given that lipidome of colonocytes is sensible to changes occurring during differentiation from stem cell to mature colonocyte, EphB2 is used to as a marker to separate stem cells from fully differentiated colonocytes. Main objectives of this project are to get more knowledge on the regulatory mechanisms involving lipid composition throughout bioinformatics and organoid culture. Methodology followed consists of several approaches such as transcriptomics, lipidomics and as already said, organoid culture. Weighted gene co-expression network analysis (WGCNA) was performed from microarray data of CRC patients to explore complex relationships between genes and phenotypes in this case lipid traits by transforming gene expression data into co-expression modules. Specially focusing on the relationship with sphingolipid SM d34:1. Results indicated higher presence of SM in the bottom of the crypt containing stem cells. Whilst through the differentiation into mature colonocytes levels of SM where lower. This observation was similar in both healthy and tumor condition. Furthermore, results suggested that the transcriptomic profile (ie. expression profile) between healthy and tumor condition is different. Consequently, regulation mechanisms of SM d34:1 among the two conditions are also different. On the other hand, to evaluate the incorporation of deuterated fatty acids in healthy colon and tumor organoids particularly between differentiated and non differentiated regions of the crypt, organoid culture experiment was performed. Unfortunately given the fact that organoid culture is a 6-8 weeklong process, it wasn’t possible to extract lipidomic results.