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Integrative analysis identifies key genes related to metastasis and a robust gene-based prognostic signature in uveal melanoma

PURPOSE: Uveal melanoma (UM) is an aggressive intraocular malignancy, leading to systemic metastasis in half of the patients. However, the mechanism of the high metastatic rate remains unclear. This study aimed to identify key genes related to metastasis and construct a gene-based signature for bett...

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Autores principales: Lei, Shizhen, Zhang, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8932077/
https://www.ncbi.nlm.nih.gov/pubmed/35300699
http://dx.doi.org/10.1186/s12920-022-01211-1
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author Lei, Shizhen
Zhang, Yi
author_facet Lei, Shizhen
Zhang, Yi
author_sort Lei, Shizhen
collection PubMed
description PURPOSE: Uveal melanoma (UM) is an aggressive intraocular malignancy, leading to systemic metastasis in half of the patients. However, the mechanism of the high metastatic rate remains unclear. This study aimed to identify key genes related to metastasis and construct a gene-based signature for better prognosis prediction of UM patients. METHODS: Weighted gene co-expression network analysis (WGCNA) was used to identify the co-expression of genes primarily associated with metastasis of UM. Univariate, Lasso-penalized and multivariate Cox regression analyses were performed to establish a prognostic signature for UM patients. RESULTS: The tan and greenyellow modules were significantly associated with the metastasis of UM patients. Significant genes related to the overall survival (OS) in these two modules were then identified. Additionally, an OS-predicting signature was established. The UM patients were divided into a low- or high-risk group. The Kaplan–Meier curve indicated that high-risk patients had poorer OS than low-risk patients. The receiver operating curve (ROC) was used to validate the stability and accuracy of the final five-gene signature. Based on the signature and clinical traits of UM patients, a nomogram was established to serve in clinical practice. CONCLUSIONS: We identified key genes involved in the metastasis of UM. A robust five-gene‐based prognostic signature was constructed and validated. In addition, the gene signature-based nomogram was created that can optimize the prognosis prediction and identify possible factors causing the poor prognosis of high-risk UM patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-022-01211-1.
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spelling pubmed-89320772022-03-23 Integrative analysis identifies key genes related to metastasis and a robust gene-based prognostic signature in uveal melanoma Lei, Shizhen Zhang, Yi BMC Med Genomics Research PURPOSE: Uveal melanoma (UM) is an aggressive intraocular malignancy, leading to systemic metastasis in half of the patients. However, the mechanism of the high metastatic rate remains unclear. This study aimed to identify key genes related to metastasis and construct a gene-based signature for better prognosis prediction of UM patients. METHODS: Weighted gene co-expression network analysis (WGCNA) was used to identify the co-expression of genes primarily associated with metastasis of UM. Univariate, Lasso-penalized and multivariate Cox regression analyses were performed to establish a prognostic signature for UM patients. RESULTS: The tan and greenyellow modules were significantly associated with the metastasis of UM patients. Significant genes related to the overall survival (OS) in these two modules were then identified. Additionally, an OS-predicting signature was established. The UM patients were divided into a low- or high-risk group. The Kaplan–Meier curve indicated that high-risk patients had poorer OS than low-risk patients. The receiver operating curve (ROC) was used to validate the stability and accuracy of the final five-gene signature. Based on the signature and clinical traits of UM patients, a nomogram was established to serve in clinical practice. CONCLUSIONS: We identified key genes involved in the metastasis of UM. A robust five-gene‐based prognostic signature was constructed and validated. In addition, the gene signature-based nomogram was created that can optimize the prognosis prediction and identify possible factors causing the poor prognosis of high-risk UM patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-022-01211-1. BioMed Central 2022-03-17 /pmc/articles/PMC8932077/ /pubmed/35300699 http://dx.doi.org/10.1186/s12920-022-01211-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Lei, Shizhen
Zhang, Yi
Integrative analysis identifies key genes related to metastasis and a robust gene-based prognostic signature in uveal melanoma
title Integrative analysis identifies key genes related to metastasis and a robust gene-based prognostic signature in uveal melanoma
title_full Integrative analysis identifies key genes related to metastasis and a robust gene-based prognostic signature in uveal melanoma
title_fullStr Integrative analysis identifies key genes related to metastasis and a robust gene-based prognostic signature in uveal melanoma
title_full_unstemmed Integrative analysis identifies key genes related to metastasis and a robust gene-based prognostic signature in uveal melanoma
title_short Integrative analysis identifies key genes related to metastasis and a robust gene-based prognostic signature in uveal melanoma
title_sort integrative analysis identifies key genes related to metastasis and a robust gene-based prognostic signature in uveal melanoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8932077/
https://www.ncbi.nlm.nih.gov/pubmed/35300699
http://dx.doi.org/10.1186/s12920-022-01211-1
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