Research Paper Volume 14, Issue 2 pp 811—825
Immunological significance of survival-related alternative splicing in uveal melanoma
- 1 Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
Received: September 21, 2021 Accepted: November 24, 2021 Published: January 19, 2022
https://doi.org/10.18632/aging.203842How to Cite
Copyright: © 2022 Kong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.