Integrated bioinformatics analysis reveals correlations of high TRIM59 expression with worse prognosis and immune infiltrates in lung adenocarcinoma

Abstract Objective: Most patients with advanced lung cancer have a poor prognosis. Recent studies have identified TRIM59 as a novel molecule that serves as a prognostic factor for the progression of non-small cell lung cancer. In the present study, we investigated the role of TRIM59 in predicting the prognosis of lung adenocarcinoma (LUAD) as well as the correlation between TRIM59 expression and immune infiltrates. Methods: We analyzed TRIM59 expression in normal and tumor tissues based on RNA-sequencing datasets from The Cancer Genome Atlas and Genotype-Tissue Expression databases. Forty-seven cases of LUAD tissues and their matching adjacent tissues were collected, and TRIM59 expression in tissue samples was demonstrated by immunohistochemistry. All tissue specimens were obtained under the approval of the Medical Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (approval No. IR2019001101; approved on April 3, 2019). The immune cell scores were calculated using the CIBERSORT database. The Tumor Immune Estimation Resource database was used to analyze the correlation between TRIM59 and immune cell activities. Results: TRIM59 was up-regulated in most cancer types. High TRIM59 expression predicted a worse prognosis in patients with LUAD (overall survival, P = 0.00096; disease-specific survival, P = 0.00056; disease-free interval, P = 0.0009; progression-free interval, P = 0.0012). Moreover, TRIM59 was highly expressed in patients with LUAD who had a poorer prognosis. TRIM59 also showed a significant correlation with the ESTIMATE score (P = 0.04) and stromal score (P = 0.005) in patients with LUAD. Notably, a significant correlation between TRIM59 and the tumor mutation burden was found in LUAD but in no other cancer types (P < 0.001). Further investigation showed that TRIM59 had a significant correlation with gene markers on neutrophils and dendritic cells. Conclusion: TRIM59 is a potential prognosticator in LUAD and may be correlated with immune cell identification, immune cell infiltration, and immunotherapy checkpoints in LUAD.