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The Microenvironment Combining with Immune Infiltration of Uveal Melanoma


 Background: Uveal melanoma (UM) is the most common intraocular malignancy in adults. Although immunotherapy provided novel options in the disease's progression, it only benefits a minority of patients. The understanding of the UM microenvironment and the potential therapeutic targets in the microenvironment is still undefined. We aimed to propose a novel classification of UM microenvironment to identify ideal biomarkers for prognosis and potential targets for effective immunotherapy.Methods: In this study, we obtained the gene expression profile of 80 UM patients from the Cancer Genome Atlas (TCGA) and calculated immune/stromal scores based on the Estimation of stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm dividing patients into the high- and low-expression groups. Then, 1024 immune-related differently expressed genes (DEGs) were selected in total following the annotation and enrichment analysis and key genes were screened by PPI network. Consequently, we conducted CIBERSORT algorithm and TIMER database to analyses the correlation between key genes and immune cells as well as utilized GeneCards database to analyses the correlation between key genes and the disease. Additionally, GSVA was performed to enrich the nonparametric and unsupervised signaling pathways of key genes and the drug sensitivity of them were predicted.Results: Based on high- and low-expression groups, we found that there were 888 up-regulated DEGs and 126 down-regulated DEGs in total, which were mainly enriched in 4 pathways in GO and 3 pathways in KEGG. Combining with the 10 genes screened by PPI, KM-plot showed that B2M and HLA-B were significantly affected the survival of UM patients. Among 22 immune cells, B2M and HLA-B were mainly corelated with 11 of them. GSVA results revealed 42 pathways significantly enriched of B2M while 41 pathways enriched of HLA-B. Finally, we predicted the Paclitaxel as the hopefully treatment for HLA-B.Conclusions: Our study not only understands deeper of fundamental biological features of microenvironment but also with potential therapeutic targets of UM.