Identification of Prognostic Alternative Splicing Signatures in Uveal Melanoma

Overview

Journal Int Ophthalmol

Specialty Ophthalmology

Date 2021 Jan 22

PMID 33479809

Citations 2

Authors

Xinyi Xie

Xinhua Zheng

Tianhua Xie

Jiping Cai

Yong Yao

Affiliations

Soon will be listed here.

Abstract

Purpose: Alternative splicing (AS) events were reportedly associated with the development of multiple cancers. The study was designed to provide a comprehensive analysis of AS events and explore their potential prognostic value in uveal melanoma (UM).

Methods: The prognostic AS events, identified based on the data of 80 UM patients obtained from The Cancer Genome Atlas, were further screened and analyzed for construction of prognostic signatures by using LASSO regression and multivariate Cox model. Kaplan-Meier survival analysis was used to evaluate the prognostic value. The AS events-related functional pathways were explored by gene set enrichment analysis (GSEA). The difference between two subgroups in terms of treatment options was investigated. The regulatory network between prognostic AS events and splicing factors (SFs) was then constructed.

Results: A total of 1014 AS events were identified as prognostic AS events. Five prognostic AS events were involved in the construction of prognostic signatures, including AKAP2/87175/AP, RGMA/32575/ES, DNASE1L1/90581/ES, BIN1/55198/ES and ERCC2/50430/AT. UM patients were then divided into two subgroups. Prognostic AS signatures had an excellent performance in predicting the survival of UM patients, with an area under curve (AUC) of 0.962. GSEA results suggested several splicing-associated mechanisms, including cellular metabolic process and apoptosis. Low-risk subgroup could be more sensitive to drugs. A higher expression of immune checkpoint genes was observed in high-risk group than in low-risk group. SFs-AS regulatory network also revealed significant association between AS events and SFs.

Conclusions: Aberrant AS events in UM patients might serve as prognostic predictors.

Citing Articles

Integrated analysis of genomic and transcriptomic data for the discovery of splice-associated variants in cancer.

Cotto K, Feng Y, Ramu A, Richters M, Freshour S, Skidmore Z Nat Commun. 2023; 14(1):1589.

PMID: 36949070 PMC: 10033906. DOI: 10.1038/s41467-023-37266-6.

Development and Validation of a Novel Metabolic Signature-Based Prognostic Model for Uveal Melanoma.

Shi K, Li X, Zhang J, Sun X Transl Vis Sci Technol. 2022; 11(5):9.

PMID: 35536719 PMC: 9100464. DOI: 10.1167/tvst.11.5.9.

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