Abstract
Uveal melanoma (UM) is a highly malignant intraocular tumor. The imbalance of alternative splicing (AS) is a landmark of tumor initiation and progression. However, there are few studies of AS in UM. Thus, this study aimed to identify a new AS-based prognostic signature and reveal its relationship with tumor-infiltrating immune cells. Univariable Cox regression analysis identified survival-related AS events. The prognostic signature was constructed using the univariable and multivariable Cox regression analyses. Kaplan-Meier survival analysis, the proportional hazard model, and receiver operating characteristic curves verified its prognostic value. Single-sample gene set enrichment analysis was used to analyze immune cell enrichment. The correlation of the risk score with tumor-infiltrating immune cells and immune checkpoint blockade (ICB) genes was examined. We screened 2886 survival-related AS events, of which five were selected to build a prognostic predictor. The risk score was positively relevant with ICB key targets (HAVCR2, IDO1, and PDCD1) and the infiltration of T cells, MDSC, and activated B cells. We provided novel and effective indices, including a risk score and clinical nomogram, for prognostic prediction in UM and discussed the potential relationship between survival-related AS events and immune cell infiltration, which is crucial for developing immune-targeted therapy to improve prognosis.
Highlights
Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults [1,2,3]
(C) The top 20 most significant survival‐relevant alternate acceptor sites (AAs), alternate donor sites (ADs), alternate terminators (ATs), alternate promoters (APs), exon skips (ESs), mutually exclusive exons (MEs) and retained introns (RIs) is shown in the bubble chart
Adopting single-sample gene set enrichment analysis [15] analyzing the correlation between 28 types of immune cells and the risk score, we found that the risk score was positive correlated with six types of immune infiltrating cells, including activated CD4 T cells, effector memory CD4 T cells, central memory CD4 T cells, activated CD8 T cells, effector memory CD8 T cells, central memory CD8 T cells, myeloid-derived suppressor cells (MDSCs), and B cells (Figure 6A–6F)
Summary
Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults [1,2,3]. A significant number of patients with UM will have systemic metastasis, with the most common metastatic organ being the liver; once metastasis occurs, survival is shortened, and surgical treatment becomes futile. Tumor immunotherapy is considered a promising treatment method and is widely used in patients with cancer. No or limited response to immunotherapy is often observed in patients with UM [5,6,7]. Based on these considerations, this study aimed to identify appropriate targets for further treatment
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