Identification and validation of tumor microenvironment-related lncRNA prognostic signature for uveal melanoma

AIM: To investigate the role of tumor microenvironment (TME)-related long non-coding RNA (lncRNA) in uveal melanoma (UM), probable prognostic signature and potential small molecule drugs using bioinformatics analysis. METHODS: UM expression profile data were downloaded from the Cancer Genome Atlas (...

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Main Authors: Chen-Lu Liao, Nan Hu, Xing-Yu Sun, Qi Zhou, Min Tian, Yang Cao, Hong-Bin Lyu
Format: Article
Language:English
Published: Press of International Journal of Ophthalmology (IJO PRESS) 2021-08-01
Series:International Journal of Ophthalmology
Subjects:
Online Access:http://ies.ijo.cn/en_publish/2021/8/20210803.pdf
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author Chen-Lu Liao
Nan Hu
Xing-Yu Sun
Qi Zhou
Min Tian
Yang Cao
Hong-Bin Lyu
author_facet Chen-Lu Liao
Nan Hu
Xing-Yu Sun
Qi Zhou
Min Tian
Yang Cao
Hong-Bin Lyu
author_sort Chen-Lu Liao
collection DOAJ
description AIM: To investigate the role of tumor microenvironment (TME)-related long non-coding RNA (lncRNA) in uveal melanoma (UM), probable prognostic signature and potential small molecule drugs using bioinformatics analysis. METHODS: UM expression profile data were downloaded from the Cancer Genome Atlas (TCGA) and bioinformatics methods were used to find prognostic lncRNAs related to UM immune cell infiltration. The gene expression profile data of 80 TCGA specimens were analyzed using the single sample Gene Set Enrichment Analysis (ssGSEA) method, and the immune cell infiltration of a single specimen was evaluated. Finally, the specimens were divided into high and low infiltration groups. The differential expression between the two groups was analyzed using the R package ‘edgeR'. Univariate, multivariate and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analyses were performed to explore the prognostic value of TME-related lncRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses were also performed. The Connectivity Map (CMap) data set was used to screen molecular drugs that may treat UM. RESULTS: A total of 2393 differentially expressed genes were identified and met the criteria for the low and high immune cell infiltration groups. Univariate Cox analysis of lncRNA genes with differential expression identified 186 genes associated with prognosis. Eight prognostic markers of TME-included lncRNA genes were established as potentially independent prognostic elements. Among 269 differentially expressed lncRNAs, 69 were up-regulated and 200 were down-regulated. Univariate Cox regression analysis of the risk indicators and clinical characteristics of the 8 lncRNA gene constructs showed that age, TNM stage, tumor base diameter, and low and high risk indices had significant prognostic value. We screened the potential small-molecule drugs for UM, including W-13, AH-6809 and Imatinib. CONCLUSION: The prognostic markers identified in this study are reliable biomarkers of UM. This study expands our current understanding of the role of TME-related lncRNAs in UM genesis, which may lay the foundations for future treatment of this disease.
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spelling doaj.art-a50f38c4ae8e416289052bfbc145e2732022-12-21T22:45:35ZengPress of International Journal of Ophthalmology (IJO PRESS)International Journal of Ophthalmology2222-39592227-48982021-08-011481151115910.18240/ijo.2021.08.0320210803Identification and validation of tumor microenvironment-related lncRNA prognostic signature for uveal melanomaChen-Lu Liao0Nan Hu1Xing-Yu Sun2Qi Zhou3Min Tian4Yang Cao5Hong-Bin Lyu6Hong-Bin Lyu. Department of Ophthalmology, Affiliated Hospital of Southwest Medical University Luzhou 646000, Sichuan Province, China. oculistlvhongbin@163.comSouthwest Medical University, Luzhou 646000, Sichuan Province, ChinaDepartment of Gynecology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, ChinaDepartment of Ophthalmology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, ChinaDepartment of Ophthalmology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, ChinaDepartment of Ophthalmology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, ChinaDepartment of Ophthalmology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, ChinaAIM: To investigate the role of tumor microenvironment (TME)-related long non-coding RNA (lncRNA) in uveal melanoma (UM), probable prognostic signature and potential small molecule drugs using bioinformatics analysis. METHODS: UM expression profile data were downloaded from the Cancer Genome Atlas (TCGA) and bioinformatics methods were used to find prognostic lncRNAs related to UM immune cell infiltration. The gene expression profile data of 80 TCGA specimens were analyzed using the single sample Gene Set Enrichment Analysis (ssGSEA) method, and the immune cell infiltration of a single specimen was evaluated. Finally, the specimens were divided into high and low infiltration groups. The differential expression between the two groups was analyzed using the R package ‘edgeR'. Univariate, multivariate and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analyses were performed to explore the prognostic value of TME-related lncRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses were also performed. The Connectivity Map (CMap) data set was used to screen molecular drugs that may treat UM. RESULTS: A total of 2393 differentially expressed genes were identified and met the criteria for the low and high immune cell infiltration groups. Univariate Cox analysis of lncRNA genes with differential expression identified 186 genes associated with prognosis. Eight prognostic markers of TME-included lncRNA genes were established as potentially independent prognostic elements. Among 269 differentially expressed lncRNAs, 69 were up-regulated and 200 were down-regulated. Univariate Cox regression analysis of the risk indicators and clinical characteristics of the 8 lncRNA gene constructs showed that age, TNM stage, tumor base diameter, and low and high risk indices had significant prognostic value. We screened the potential small-molecule drugs for UM, including W-13, AH-6809 and Imatinib. CONCLUSION: The prognostic markers identified in this study are reliable biomarkers of UM. This study expands our current understanding of the role of TME-related lncRNAs in UM genesis, which may lay the foundations for future treatment of this disease.http://ies.ijo.cn/en_publish/2021/8/20210803.pdfuveal melanomatumor microenvironmentlncrnaprognosisconnectivity mapbioinformatics
spellingShingle Chen-Lu Liao
Nan Hu
Xing-Yu Sun
Qi Zhou
Min Tian
Yang Cao
Hong-Bin Lyu
Identification and validation of tumor microenvironment-related lncRNA prognostic signature for uveal melanoma
International Journal of Ophthalmology
uveal melanoma
tumor microenvironment
lncrna
prognosis
connectivity map
bioinformatics
title Identification and validation of tumor microenvironment-related lncRNA prognostic signature for uveal melanoma
title_full Identification and validation of tumor microenvironment-related lncRNA prognostic signature for uveal melanoma
title_fullStr Identification and validation of tumor microenvironment-related lncRNA prognostic signature for uveal melanoma
title_full_unstemmed Identification and validation of tumor microenvironment-related lncRNA prognostic signature for uveal melanoma
title_short Identification and validation of tumor microenvironment-related lncRNA prognostic signature for uveal melanoma
title_sort identification and validation of tumor microenvironment related lncrna prognostic signature for uveal melanoma
topic uveal melanoma
tumor microenvironment
lncrna
prognosis
connectivity map
bioinformatics
url http://ies.ijo.cn/en_publish/2021/8/20210803.pdf
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