Construction and validation of a novel prognostic signature for uveal melanoma based on five metabolism-related genes

Background: Uveal melanoma (UM) is the most aggressive intraocular tumor worldwide. Accurate prognostic models are urgently needed. The present research aimed to construct and validate a prognostic signature is associated with overall survival (OS) for UM patients based on metabolism-related genes...

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Main Authors: Han Zhao, Yun Chen, Peijun Shen, Lan Gong
Format: Article
Language:English
Published: AIMS Press 2021-09-01
Series:Mathematical Biosciences and Engineering
Subjects:
Online Access:https://www.aimspress.com/article/doi/10.3934/mbe.2021399?viewType=HTML
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author Han Zhao
Yun Chen
Peijun Shen
Lan Gong
author_facet Han Zhao
Yun Chen
Peijun Shen
Lan Gong
author_sort Han Zhao
collection DOAJ
description Background: Uveal melanoma (UM) is the most aggressive intraocular tumor worldwide. Accurate prognostic models are urgently needed. The present research aimed to construct and validate a prognostic signature is associated with overall survival (OS) for UM patients based on metabolism-related genes (MRGs). Methods: MRGs were obtained from molecular signature database (MSigDB). The gene expression profiles and patient clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. In the training datasets, MRGs were analyzed through univariate Cox regression analyses and least absolute shrinkage and selection operator (LASSO) Cox analyses to build a prognostic model. The GSE84976 was treated as the validation cohort. In addition, time-dependent receiver operating characteristic (ROC) and Kaplan-Meier survival curve analyses the reliability of the developed model. Then, gene set enrichment analysis (GSEA) was used for gene enrichment analysis. Nomogram that combined the five-gene signature was used to evaluate the predictive OS value of UM patients. Results: Five MRGs were identified and used to establish the prognostic model for UM patients. The model was successfully validated using the testing cohort. Moreover, ROC analysis demonstrated a strong predictive ability that our prognostic signature had for UM prognosis. Multivariable Cox regression analysis revealed that the risk model was an independent predictor of prognosis. UM patients with a high-risk score showed a higher level of immune checkpoint molecules. Conclusion: We established a novel metabolism-related signature that could predict survival and might be therapeutic targets for the treatment of UM patients.
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spelling doaj.art-ff4021cbc2094952bfbe48cac45e73802022-12-22T04:04:05ZengAIMS PressMathematical Biosciences and Engineering1551-00182021-09-011868045806310.3934/mbe.2021399Construction and validation of a novel prognostic signature for uveal melanoma based on five metabolism-related genesHan Zhao 0Yun Chen1Peijun Shen2Lan Gong31. Department of Ophthalmology, Eye, Ear, Nose, and Throat Hospital of Fudan University, Shanghai, China 2. Laboratory of Myopia, NHC Key Laboratory of Myopia (Fudan University), Chinese Academy of Medical Sciences, Shanghai, China 3. Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China4. Department of Stomatology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China5. Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Henan, China1. Department of Ophthalmology, Eye, Ear, Nose, and Throat Hospital of Fudan University, Shanghai, China 2. Laboratory of Myopia, NHC Key Laboratory of Myopia (Fudan University), Chinese Academy of Medical Sciences, Shanghai, China 3. Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, ChinaBackground: Uveal melanoma (UM) is the most aggressive intraocular tumor worldwide. Accurate prognostic models are urgently needed. The present research aimed to construct and validate a prognostic signature is associated with overall survival (OS) for UM patients based on metabolism-related genes (MRGs). Methods: MRGs were obtained from molecular signature database (MSigDB). The gene expression profiles and patient clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. In the training datasets, MRGs were analyzed through univariate Cox regression analyses and least absolute shrinkage and selection operator (LASSO) Cox analyses to build a prognostic model. The GSE84976 was treated as the validation cohort. In addition, time-dependent receiver operating characteristic (ROC) and Kaplan-Meier survival curve analyses the reliability of the developed model. Then, gene set enrichment analysis (GSEA) was used for gene enrichment analysis. Nomogram that combined the five-gene signature was used to evaluate the predictive OS value of UM patients. Results: Five MRGs were identified and used to establish the prognostic model for UM patients. The model was successfully validated using the testing cohort. Moreover, ROC analysis demonstrated a strong predictive ability that our prognostic signature had for UM prognosis. Multivariable Cox regression analysis revealed that the risk model was an independent predictor of prognosis. UM patients with a high-risk score showed a higher level of immune checkpoint molecules. Conclusion: We established a novel metabolism-related signature that could predict survival and might be therapeutic targets for the treatment of UM patients.https://www.aimspress.com/article/doi/10.3934/mbe.2021399?viewType=HTMLuveal melanomametabolismtcgageoprognostic modelimmune cell infiltration
spellingShingle Han Zhao
Yun Chen
Peijun Shen
Lan Gong
Construction and validation of a novel prognostic signature for uveal melanoma based on five metabolism-related genes
Mathematical Biosciences and Engineering
uveal melanoma
metabolism
tcga
geo
prognostic model
immune cell infiltration
title Construction and validation of a novel prognostic signature for uveal melanoma based on five metabolism-related genes
title_full Construction and validation of a novel prognostic signature for uveal melanoma based on five metabolism-related genes
title_fullStr Construction and validation of a novel prognostic signature for uveal melanoma based on five metabolism-related genes
title_full_unstemmed Construction and validation of a novel prognostic signature for uveal melanoma based on five metabolism-related genes
title_short Construction and validation of a novel prognostic signature for uveal melanoma based on five metabolism-related genes
title_sort construction and validation of a novel prognostic signature for uveal melanoma based on five metabolism related genes
topic uveal melanoma
metabolism
tcga
geo
prognostic model
immune cell infiltration
url https://www.aimspress.com/article/doi/10.3934/mbe.2021399?viewType=HTML
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AT yunchen constructionandvalidationofanovelprognosticsignatureforuvealmelanomabasedonfivemetabolismrelatedgenes
AT peijunshen constructionandvalidationofanovelprognosticsignatureforuvealmelanomabasedonfivemetabolismrelatedgenes
AT langong constructionandvalidationofanovelprognosticsignatureforuvealmelanomabasedonfivemetabolismrelatedgenes