An autophagy-related prognostic signature associated with immune microenvironment features of uveal melanoma.

2021 
Autophagy is involved in cancer initiation and progression but its role in uveal melanoma (UM) has rarely been investigated. Herein, we built an autophagy-related gene (ARG) risk model for UM patients using univariate Cox regression and the least absolute shrinkage and selection operator regression model and filtered out 9 prognostic ARGs based on a cohort from The Cancer Genome Atlas (TCGA). Survival and receiver operating characteristic curve analysis of TCGA and four other independent UM cohorts (GSE22138, GSE27831, GSE39717 and GSE84976) demonstrated that the ARG-signature possessed robust and steady prognostic predictive ability. Risk scores were calculated for patients included in our study and patients with higher risk scores showed worse clinical outcomes. The expression of 9 ARGs were significantly associated with clinical and molecular features (including risk score) and overall survival of UM patients. Furthermore, we utilized univariate and multivariate Cox regression analysis to determine the independent prognostic ability of the ARG-signature. Functional enrichment analysis showed the ARG-signature was correlated with several immune-related processes and pathways like T cell activation and the T cell receptor signaling pathway. Gene set enrichment analysis identified tumor hallmarks including angiogenesis, oxidative phosphorylation, and the IL6-JAK-STAT3-signaling and reactive oxygen species pathways and were enriched in high-risk UM patients. Finally, infiltration of several immune cells and immune-related scores were found to be significantly associated with the ARG-signature. In conclusion, the ARG-signature might represent a strong predictor for evaluating the prognosis and immune infiltration of UM patients.
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