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Immunological significance of survival-related alternative splicing in uveal melanoma

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 wi...

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Detalles Bibliográficos
Autores principales: Kong, Deqian, Li, Li, Wang, Huajun, Li, Ke, Zheng, Guangying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8833124/
https://www.ncbi.nlm.nih.gov/pubmed/35051904
http://dx.doi.org/10.18632/aging.203842
Descripción
Sumario: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.