A MiRNA-based Signature is Associated With Tumor Mutational Burden in Colon Adenocarcinoma

Abstract

Background:Tumor mutation burden (TMB) has become an independent biomarker for predicting the response of Immune checkpoint inhibitors.MiRNA plays an important role in cancer-related immune regulation but the relationship between expression of miRNA and TMB is unclear in colon adenocarcinoma (COAD).Method:The transcriptome profiling data, clinical data, mutation annotation data and miRNA expression profiles for cases with COAD were downloaded from TCGA database, and then COAD samples were randomly divided into training set and test set. The differential expression miRNAs of high and low TMB group in training set was obtained as a signature by the least absolute shrinkage and selection operator (LASSO) logistic regression, and it was verified in test set. UsingLASSO method, principal component analysis (PCA) and ROC to verify the credibility of signature.In addition, the correlation betweenthemiRNA-based signature and immune checkpoints was performed.In the end, enrichment analysis of the miRNAs in signature was performed to explore the biological function.Results:18 differential expression miRNAswere obtainedaccording to LASSO method. According to LASSO method, principal component analysis (PCA) and ROC, we found that the credibility of signature, and the signature can discriminate the high and low TMB level. Furthermore, the results of correlation between the 18-miRNA-based signature and immune checkpoints showed that the miRNA-based model has a strong positive correlation with TMB, weak positive correlation with CTLA4 and CD274 (PD-L1). However, there is no correlation between the model and SNCA (PD-1).Finally, enrichment analysis of the 18miRNAs demonstrated that the 18 miRNAs were involved in process of immunity and cancer pathways.Conclusion:We established a novel miRNA-based signature integrating expression of miRNAs and TMB levels. The 18-miRNA-based signature can effectively predict and discriminate the TMB levels in COAD, and provides apotential guide of ICIs treatment.