Integrative modeling of multi-omics data for predicting tumor mutation burden in lung cancer patients

Abstract

Background Immunotherapy has been widely used in the treatment of lung cancer, and one of the most effective biomarker for the prognosis of immunotherapy currently is tumor mutation burden (TMB). Although whole-exome sequencing (WES) could be utilized to assess TMB, several problems prevent its routine clinical application. Methods To develop a simplified TMB prediction model, patients with lung adenocarcinoma (LUAD) in The Cancer Genome Atlas (TCGA) were randomly split into training and validation cohorts, and categorized into TMB-high (TMB-H) and TMB-low (TMB-L) groups respectively. Results Based on the 610 differentially expressed genes, 50 differentially expressed miRNAs and 58 differentially methylated CpG sites between TMB-H and TMB-L patients, we constructed 4 predictive signatures and established TMB prediction model through machine learning methods that integrating the expression or methylation profiles of 7 genes, 7 miRNAs and 6 CpG sites. The multi-omics model exhibited excellent performance in predicting TMB with the area under curve (AUC) of 0.911 in the training cohort and 0.859 in the validation cohort. Besides, the significant correlation between the multi-omics model score and TMB was observed. Conclusions In summary, we developed a prognostic TMB prediction model by integrating multi-omics data in patients with LUAD, which might facilitate the further development of quantitative real time-polymerase chain reaction (qRT-PCR) based TMB detection assay.