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Development and validation of an oxidative stress‑related prognostic signature in osteosarcoma: A combination of molecular experiments and bioinformatics
Osteosarcoma (OS) is one of the most prevalent malignancies with a bad prognosis. Oxidative stress is closely associated with various type of cancer. The present study aimed to establish an oxidative stress-related gene prognostic signature. Supported by The Cancer Genome Atlas and Gene Expression O...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10236143/ https://www.ncbi.nlm.nih.gov/pubmed/37274481 http://dx.doi.org/10.3892/ol.2023.13865 |
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author | Xie, Bin Tan, Shiyong Li, Chao Liang, Junyang |
author_facet | Xie, Bin Tan, Shiyong Li, Chao Liang, Junyang |
author_sort | Xie, Bin |
collection | PubMed |
description | Osteosarcoma (OS) is one of the most prevalent malignancies with a bad prognosis. Oxidative stress is closely associated with various type of cancer. The present study aimed to establish an oxidative stress-related gene prognostic signature. Supported by The Cancer Genome Atlas and Gene Expression Omnibus, the least absolute shrinkage and selection operator regression, Cox regression, receiver operating characteristic curves and Kaplan-Meier survival analysis were used to construct and validate a prognostic signature and the derived risk score. Tumor microenvironment scores and immune infiltration levels in OS were calculated. Correlation between these parameters and risk score was analyzed. In addition, single analysis of each hub gene was performed. Finally, a series of molecular experiments was used to detect the role of MAP3K5 (one of the hub genes) in OS. A total of five genes most associated with OS prognosis were identified as independent predictors, namely catalase (CAT), mitogen-activated protein kinase 1 (MAPK1), glucose-6-phosphate dehydrogenase (G6PD), mitogen-activated protein kinase kinase kinase 5 (MAP3K5) and C-C motif chemokine ligand 2 (CCL2). Based on the signature, higher risk score indicated poorer prognosis. Nomogram performed well and reliably predicted 3- and 5-year survival rate in OS. Patients with increasing risk scores had higher tumor purity and lower immune infiltration levels. Compared with an osteoblast cell line, the expression of CAT, CCL2, MAPK1 and G6PD was upregulated and MAP3K5 was downregulated. MAP3K5 inhibited cellular proliferation and motility, promoted cellular apoptosis and induced reactive oxygen species generation. Overall, the signature could effectively predict the prognosis of patients with OS and were expected to be potential biomarkers. And it provided new ideas for understanding the interactions between oxidative stress and OS. |
format | Online Article Text |
id | pubmed-10236143 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-102361432023-06-03 Development and validation of an oxidative stress‑related prognostic signature in osteosarcoma: A combination of molecular experiments and bioinformatics Xie, Bin Tan, Shiyong Li, Chao Liang, Junyang Oncol Lett Articles Osteosarcoma (OS) is one of the most prevalent malignancies with a bad prognosis. Oxidative stress is closely associated with various type of cancer. The present study aimed to establish an oxidative stress-related gene prognostic signature. Supported by The Cancer Genome Atlas and Gene Expression Omnibus, the least absolute shrinkage and selection operator regression, Cox regression, receiver operating characteristic curves and Kaplan-Meier survival analysis were used to construct and validate a prognostic signature and the derived risk score. Tumor microenvironment scores and immune infiltration levels in OS were calculated. Correlation between these parameters and risk score was analyzed. In addition, single analysis of each hub gene was performed. Finally, a series of molecular experiments was used to detect the role of MAP3K5 (one of the hub genes) in OS. A total of five genes most associated with OS prognosis were identified as independent predictors, namely catalase (CAT), mitogen-activated protein kinase 1 (MAPK1), glucose-6-phosphate dehydrogenase (G6PD), mitogen-activated protein kinase kinase kinase 5 (MAP3K5) and C-C motif chemokine ligand 2 (CCL2). Based on the signature, higher risk score indicated poorer prognosis. Nomogram performed well and reliably predicted 3- and 5-year survival rate in OS. Patients with increasing risk scores had higher tumor purity and lower immune infiltration levels. Compared with an osteoblast cell line, the expression of CAT, CCL2, MAPK1 and G6PD was upregulated and MAP3K5 was downregulated. MAP3K5 inhibited cellular proliferation and motility, promoted cellular apoptosis and induced reactive oxygen species generation. Overall, the signature could effectively predict the prognosis of patients with OS and were expected to be potential biomarkers. And it provided new ideas for understanding the interactions between oxidative stress and OS. D.A. Spandidos 2023-05-12 /pmc/articles/PMC10236143/ /pubmed/37274481 http://dx.doi.org/10.3892/ol.2023.13865 Text en Copyright: © Xie et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Xie, Bin Tan, Shiyong Li, Chao Liang, Junyang Development and validation of an oxidative stress‑related prognostic signature in osteosarcoma: A combination of molecular experiments and bioinformatics |
title | Development and validation of an oxidative stress‑related prognostic signature in osteosarcoma: A combination of molecular experiments and bioinformatics |
title_full | Development and validation of an oxidative stress‑related prognostic signature in osteosarcoma: A combination of molecular experiments and bioinformatics |
title_fullStr | Development and validation of an oxidative stress‑related prognostic signature in osteosarcoma: A combination of molecular experiments and bioinformatics |
title_full_unstemmed | Development and validation of an oxidative stress‑related prognostic signature in osteosarcoma: A combination of molecular experiments and bioinformatics |
title_short | Development and validation of an oxidative stress‑related prognostic signature in osteosarcoma: A combination of molecular experiments and bioinformatics |
title_sort | development and validation of an oxidative stress‑related prognostic signature in osteosarcoma: a combination of molecular experiments and bioinformatics |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10236143/ https://www.ncbi.nlm.nih.gov/pubmed/37274481 http://dx.doi.org/10.3892/ol.2023.13865 |
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