Clinical Treatment Of Colorectal Mucinous Adenocarcinoma Could Be Discriminate From Adenocarcinoma: Genesis And Immune Microenvironment Differences On Transcript Level

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. The study aims to explore the difference between MC and AD of CRC on transcriptome level, for possibility of treating colorectal MC precisely. 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 some others may be associated with unique immune progress. 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 This study suggests that clinical treatments for colorectal MC should be differentiated from AD. Further exploration of enterocyte (goblet cell) differentiation with tumor genesis and the distinct immune progression of MC may help to identify key therapeutic targets for colorectal MC. Further research into the application of immunotherapy to colorectal MC is needed.