Autophagy-Related Long Non-coding RNA Signature as Indicators for the Prognosis of Uveal Melanoma.

Yi Cui,Jing Chen,Mi Zheng,Nuo Xu

doi:10.3389/fgene.2021.625583

Yi Cui, Jing Chen + Show 2 more

Open Access

https://doi.org/10.3389/fgene.2021.625583

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Abstract

This study aimed to develop an autophagy-associated long non-coding RNA (lncRNA) signature to predict the prognostic outcomes of uveal melanoma (UM). The data of UM from The Cancer Genome Atlas (TCGA) were enrolled to obtain differentially expressed genes (DEGs) between metastasizing and non-metastasizing UM patients. A total of 13 differentially expressed autophagy genes were identified and validated in Gene Expression Omnibus, and 11 autophagy-related lncRNAs were found to be associated with overall survival. Through performing least absolute shrinkage and selection operator regression analyses, a six-autophagy-related lncRNA signature was built, and its efficacy was confirmed by receiver-operating characteristic, Kaplan–Meier analysis, and univariate and multivariate Cox regression analyses. A comprehensive nomogram was established and its clinical net benefit was validated by decision curve analysis. GSEA revealed that several biological processes and signaling pathways including Toll-like receptor signaling pathway, natural killer cell-mediated cytotoxicity, and B- and T-cell receptor signaling pathway were enriched in the high-risk group. CIBERSORT results showed that the signature was related to the immune response especially HLA expression. This signature could be deployed to assist clinicians to identify high-risk UM patients and help scientists to explore the molecular mechanism of autophagy-related lncRNAs in UM pathogenesis.

Highlights

Uveal melanoma (UM) is the most common and aggressive malignant neoplasm of the eye in adults, and up to 50–62% of UM patients will suffer from metastasis (Kujala et al, 2003; Amaro et al, 2017; Kaliki and Shields, 2017)
Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of all differentially expressed genes (DEGs) are shown in Supplementary Figure 1
GO and KEGG analyses of autophagy DEGs revealed that these DEGs were mainly enriched in cellular responses to starvation and extracellular stimulus and in relevant autophagy processes (Figures 2C,D)

Summary

Introduction

Uveal melanoma (UM) is the most common and aggressive malignant neoplasm of the eye in adults, and up to 50–62% of UM patients will suffer from metastasis (Kujala et al, 2003; Amaro et al, 2017; Kaliki and Shields, 2017). Local interventions including transpupillary thermotherapy (Mashayekhi et al, 2015), photodynamic thermotherapy (Cerman and Cekic, 2015), brachytherapy (Collaborative Ocular Melanoma Study Group, 2006), and surgical enucleation (Shields and Shields, 2015) are the main strategies to treat the primary tumor, but the overall prognosis for metastatic UM remains poor. It is imperative to identify high-risk UM patients with poor prognosis. Clinical features including patient age, tumor apical height, involvement of ciliary body, and largest basal diameter (LBD) of the tumor have been identified as prognostic factors for Autophagy LncRNA for UM metastasis (Chew et al, 2015; Correa and Augsburger, 2016). The prognostic value of long non-coding RNAs (lncRNAs) in UM has not been fully explored

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