Transcriptomic Landscape Of Colorectal Mucinous Adenocarcinoma Has Similarity With Intestinal Goblet Cells Differentiation

Abstract

Abstract Background Mucinous adenocarcinoma (MC) of colorectal cancer (CRC) differs from adenocarcinoma (AD) in clinical features and molecular characteristics. Current treatment of colorectal MC isn't precise enough and the molecular characteristics remain unclear. Methods We accessed the data of CRC patients from The Cancer Genome Atlas (TCGA) database, then we performed differential analysis and weighted gene co-expression network analysis (WGCNA) to identify the differential hub RNAs between colorectal MC and AD. Functional enrichment analysis, RNAs co-expression networks, risk score based on least absolute shrinkage and selection operator (LASSO) regression model and validation in Gene Expression Omnibus (GEO) database, survival analysis were also performed. Finally, differential hub lncRNAs and hub RNA of significant module were validated by quantitative real time PCR (qRT-PCR) among different colon cancer cell lines. Results In total, we found 1680 differential expressed RNAs (DERs) and 4 significant modules (darkred, magenta, lightstellblue1, tan) comparing colorectal MC (52, 13.3%) with AD (340, 86.7%). From the functional enrichment analysis and RNAs co-expression networks, the darkred module was considered as a mucin-associated module, while others may be associated with other features of colorectal MC. Construction of logistic regression model and calculation of risk score based on differential hub RNAs in darkred module showed acceptable result in both TCGA and GEO data. Survival analysis suggested that many differential hub RNAs were positive and correlated with better survival. Finally, 8 differential hub RNAs in the darkred module (CTD-2547H18.1, CTD-2589M5.4, RP11-234B24.2, LA16c-321D4.2, LINC00261, RP11-25K19.1, COLCA1 and CAPN9) were validated by qRT-PCR. Except for LA16c-321D4.2 and COLCA1, all other RNAs showed higher expression levels in mucin-producing colorectal cell lines (Ls174T, HT-29 and T84). Conclusion The study strengthens the findings of distinct molecular features between MC and AD in CRC and identifies potential marker RNAs making colorectal MC unique from AD. The genesis of colorectal MC may be related to the differentiation fate of intestinal goblet cells.