Comprehensive Analysis of TRIM Family-based Signature in LUAD Progression and Immunotherapy

Abstract

Abstract Purpose: Within the ubiquitination process, E3 ligases function profoundly since they decide the final step of target specificity. As the largest subfamily of E3 ligases, tripartite motif (TRIM) family genes play pivotal roles in tumor progression and immune response, however, lacking systematic exploration of the expression patterns and clinical correlations in lung adenocarcinoma (LUAD). We aim to comprehensively analyze the TRIM expression profile in LUAD and establish a TRIM family–based prognostic risk model. Methods: We enrolled 1299 cases from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets for risk model training and validation. Another 38 LUAD tissues were collected for validation. Bioinformatic methods and immunofluorescent staining were utilized to illustrated the related Biological characteristics, mutation tendency, immune profile and predicted immunotherapy response. Results: After Cox proportional hazards regression analyses, we established a 3 TRIM gene-based risk model by TCGA dataset. The risk model divided patients into high and low score groups showing different overall survival (OS), being an independent prognostic factor irrespective of other clinical features. And the stability was estimated in GEO validation datasets and even tissues at protein level. Further explorations demonstrated patients within high risk group showed tendency to more EGFR mutation and severer immune suppressive status. Moreover, the risk model was markedly correlated with diverse immunotherapy response markers. Conclusion: We constructed the first TRIM-based prognostic risk model for LUAD OS prediction and demonstrated the relationships between the model and LUAD immune characteristics. The risk model might assist the clinical application of immunotherapies.