Abstract
The tumor microenvironment is an important factor for the immunotherapy of tumor patients. The sequenced transcriptome data can be used to describe the tumor microenvironment and various immune subtypes. We exploited published data on patients with uveal melanoma (UVM) to identify immune subtypes. Based on the immune-related gene sets of 80 patients with UVM in the TCGA database, we used consensus clustering to identify two immune subgroups. In the two immune subtypes, we analyzed clinical characteristics and immune infiltration. Class1 has low immune infiltration, contains memory B cells, Th2 cells, Th17 cells, eosinophils, natural killer cells, and has a better prognosis. Class2 has higher immune infiltration. CD8+ T cells, Th1 cells, MDSCs, and Dendritic cells are enriched in class2, which has strong cytolytic activity, high expression of immune checkpoint genes, and poor outcome. Moreover, we have developed and verified an immune characteristic model that can predict the prognosis of patients well. Through this model, we screened prostaglandin-endoperoxide synthase 2 (PTGS2) as the therapeutic target of UVM. Treatment of choroidal melanoma cell line (OCM1) cells with celecoxib (an inhibitor of PTGS2) effectively inhibits cell growth, proliferation, and promotes apoptosis. Our results show the immunological heterogeneity of UVM patients and also provide an ideal therapeutic target for the future treatment design of patients.
Highlights
Uveal melanoma (UVM) is one of the most common primary intraocular malignant tumors, originating in the choroid, ciliary body, or iris (Willson et al, 2001; Chattopadhyay et al, 2016; Kaliki and Shields, 2017)
The data for this study came from two databases (Table 1): The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). 80 uveal melanoma (UVM) patients came from the TCGA database, containing RNA-seq data, somatic mutations, copy number variations (CNVs), DNA methylation and clinical sample data
The identification of immune subtypes in UVM establishes a risk prediction model, which effectively predicts the prognosis of patients
Summary
Uveal melanoma (UVM) is one of the most common primary intraocular malignant tumors, originating in the choroid, ciliary body, or iris (Willson et al, 2001; Chattopadhyay et al, 2016; Kaliki and Shields, 2017). It is estimated that there are about 7000 new cases of UVM every year worldwide, with an incidence rate of about 4.3 parts per million (Schank and Hassel, 2019). The 5-year survival rate of patients is 50–70%. Precise Therapeutic Targets in UVM in higher mortality (Willson et al, 2001; Kaliki and Shields, 2017). The treatment of tumor has been improved continuously, there is still no standard treatment method for metastatic UVM
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