IDDF2018-ABS-0104 Molecular insights into colon mucinous adenocarcinoma

Abstract

Background Mucinous adenocarcinoma (MAC) is a histological subtype of colorectal cancer (CRC), in which account for 5%–15% of all primary CRC. MAC is characterised by the formation of a tumour comprised of >50% mucin. The prognostic value of MAC remains controversial; several studies report that MAC has a worse prognosis than nonmucinous adenocarcinoma (non-MAC), while others are not. Thus, it is important to decipher the molecular signature of MAC to better understand the unfamiliar subtype of the disease and improve the individualised management of patients with MAC. Methods Here, we comprehensively characterised the somatic mutation, genome-wide transcriptional (mRNA and miRNA), and epigenetic (DNA methylation) profiles of the MAC, combined with correlative analyses of expression, methylation, and clinical data from the Cancer Genome Atlas. Differentially expressed gene (DEGs, false discovery rate (FDR) adjusted P-value 2 ) analysis between MAC and non-MAC was performed by DEGSeq package for R/Bioconductor. Significantly differentially methylated site (DMS, FDR adjusted P-value 0.2) was performed by limma package for R/Bioconductor. Results Results showed that MAC harbours 3366 frequent mutational gene sets (FMGSs, apriori method), in sharp contrast to only 94 in non-MAC. Three-fold higher BRAF mutation rate in MAC than non-MAC was observed, and this may account for a worse prognosis in MAC. Notably, we found ATM had the same high mutation rate as TP53 in MAC, thus rescue of ATM was rather important because ATM acts upstream of TP53. In addition, hundreds of DEGs such as AQP3, MUC2, and FCGBP and 4 differentially expressed miRNAs were determined between MAC and non-MAC. Additionally, 1,926 DMSs that were associated with inflammatory response, cell adhesion, neutrophil chemotaxis, and immune response were identified as well. Conclusions The huge molecular difference exists between MAC and non-MAC inspires us treating CRC in a more careful manner because we are driving toward a new era of precision medicine. In other words, the medical decision making used in MAC cannot simply copy from strategy adopted in non-MAC.