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Erschienen in: International Ophthalmology 4/2021

21.01.2021 | Original Paper

Identification of prognostic alternative splicing signatures in uveal melanoma

verfasst von: Xinyi Xie, Xinhua Zheng, Tianhua Xie, Jiping Cai, Yong Yao

Erschienen in: International Ophthalmology | Ausgabe 4/2021

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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.
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Metadaten
Titel
Identification of prognostic alternative splicing signatures in uveal melanoma
verfasst von
Xinyi Xie
Xinhua Zheng
Tianhua Xie
Jiping Cai
Yong Yao
Publikationsdatum
21.01.2021
Verlag
Springer Netherlands
Erschienen in
International Ophthalmology / Ausgabe 4/2021
Print ISSN: 0165-5701
Elektronische ISSN: 1573-2630
DOI
https://doi.org/10.1007/s10792-021-01699-z

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