Association of a 20-lncRNA signature with mutation load of colon adenocarcinoma and immune microenvironment

Abstract Purpose Tumor mutation burden (TMB) is an emerging biomarker for predicting immune checkpoint inhibitors (ICI). However, the role of TMB associated with long non-coding RNAs (lncRNAs) expression was not clear for preexisting immunity in colon adenocarcinoma (COAD). Methods The mutation data for COAD was downloaded from the Cancer Genome atlas (TCGA) database. A set of differentially expressed lncRNAs (DE lncRNAs) were identified between high or low TMB colon adenocarcinoma samples through differential expression analysis. The absolute shrinkage and selection operator (LASSO) method was used to define a subset of the DE lncRNAs as a “signature” for predicting TMB levels in the training cohort. After validating the signature on a test cohort, its potential correlations with the indicators of the efficacy of anti-immune checkpoint therapy were explored. Gene set variation analysis (GSVA) was carried out to explore the biological functions between high and low signature DE lncRNAs sample groups. Results A signature comprising 20 DE lncRNAs predicted TMB levels was identified by lasso method. And the model was with high accuracy in the training cohort (AUC=0.92) and test cohort (AUC=0.93). Moreover, the signature was also associated with T-effector and interferon-γ gene signature, expression of PDCD1, CD274, CTLA4, as well as abundance of TILs. Tumors receiving a low score for the 20-lncRNA signature received a high GSVA score for multiple immune-related pathways. Conclusions The 20-lncRNA signature can accurately predict TMB in colon adenocarcinoma and is associated with known indicators of immune checkpoint inhibitor efficacy and preexisting immunity.