High TRIM59 Expression Predicts Adverse Outcomes and Is Correlated with Immune Infiltrates in Lung Adenocarcinoma

Tripartite motif (TRIM) 59 protein, a cancer-associated E3 ubiquitin ligase, plays important roles in various biological processes including innate immune response, autophagy, cell cycle, glycolysis and tumorigenicity. The mechanism of autophagy regulated by TRIM59 in non-small cell lung cancer (NSCLC) has been elucidated clearly. It has been demonstrated that TRIM59 was a novel molecule prognostic factor of NSCLC and frequently up-regulated in NSCLC patients, that was verified in The Cancer Genome Atlas (TCGA) datasets. Nevertheless, it still remains unclear of the correlation between TRIM59 expression and immune infiltrates as well as the predictive value of TRIM59 in lung adenocarcinoma (LUAD). In this study, analysis of TRIM59 expression in normal and tumor tissues indicated that TRIM59 was up-regulated in most tumor tissues based on RNA-seq datasets from TCGA and Genotype-Tissue Expression (GTEx) databases. The correlation analysis between TRIM59 expression and overall survival (OS), disease-specifical survival (DSS), disease-free interval (DFI) or progress free interval (PFI), suggested that high TRIM59 expression predicted adverse outcomes in LUAD (OS: P=0.00096; DSS: P=0.00056; DFI: P=0.0009; PFI: P=0.0012). The correlation analysis between TRIM59 and immune checkpoints revealed that TRIM59 was significantly correlated with most of immune checkpoints in TCGA database, and TRIM59 had significant correlation with TMB (P<0001), ESITIMATE score (P=0.04) or stromal score (P=0.005) in LUAD. Further investigation demonstrated that the significantly negative correlation between TRIM59 expression and tumor purity was only shown in LUAD (P=0.027). It was found that TRIM59 had significant correlation with gene markers on macrophage and neutrophil in Tumor Immune Estimation Resource (TIMER) database, indicating that TRIM59 expression in LUAD played an essential regulatory role in tumor immune progress including infiltration of macrophage and neutrophil. Functional enrichment analysis as well as correlation analysis between TRIM59 and clinical characteristics of LUAD patients was also performed in our report. Combined with previously reported prognostic role of TRIM59 in NSCLC, our results proved that TRIM59 is a prognosticator for LUAD and is correlated with immune infiltrates in LUAD. Funding Statement: This work was supported by the National Natural Science Foundation of China (81703072), The Natural Science Foundation of Zhejiang Province (LQ21H160027). Declaration of Interests: The authors have no conflict of interests.