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Identification and validation of a five-gene prognostic signature based on bioinformatics analyses in breast cancer
BACKGROUND: This study aimed to identify prognostic signatures to predict the prognosis of breast cancer (BRCA) patients based on a series of comprehensive analyses of gene expression data. METHODS: The RNA-sequencing expression data and corresponding BRCA patient clinical data were collected from t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9898304/ https://www.ncbi.nlm.nih.gov/pubmed/36747547 http://dx.doi.org/10.1016/j.heliyon.2023.e13185 |
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author | Du, Xin-jie Yang, Xian-rong Wang, Qi-cai Lin, Guo-liang Li, Peng-fei Zhang, Wei-feng |
author_facet | Du, Xin-jie Yang, Xian-rong Wang, Qi-cai Lin, Guo-liang Li, Peng-fei Zhang, Wei-feng |
author_sort | Du, Xin-jie |
collection | PubMed |
description | BACKGROUND: This study aimed to identify prognostic signatures to predict the prognosis of breast cancer (BRCA) patients based on a series of comprehensive analyses of gene expression data. METHODS: The RNA-sequencing expression data and corresponding BRCA patient clinical data were collected from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets. Firstly, the differently expressed genes (DEGs) related to prognosis between tumor tissues and normal tissues were ascertained by performing R package “limma”. Secondly, the DEGs were used to construct a polygenic risk scoring model by the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator Cox regression (Lasso-cox) analysis method. Thirdly, survival analysis was performed to investigate the risk score values in the TCGA cohort. And the enrichment analysis, immune cell infiltration levels analysis, and protein-protein internet (PPI) analysis were performed. Simultaneously, the GEO cohort was used to validate the model. Lastly, we constructed a nomogram to explore the influence of polygenic risk score and other clinical factors on the survival probability of patients with BRCA. RESULTS: A total of 1000 DEGs including 396 upregulated genes and 604 downregulated genes were identified from the TCGA-BRCA dataset. We obtained 5 prognosis-related genes, as the key biomarkers by Lasso-cox analysis (FBXL19, HAGHL, PHKG2, PKMYT1, and TXNDC17), all of which were significantly upregulated in breast tumors. The prognostic prediction of the 5 genes model was great in training and validation cohorts. Moreover, the high-risk group had a poorer prognosis. The Cox regression analysis showed that the comprehensive risk score for 5 genes was an independent prognosis factor. CONCLUSION: The 5 genes risk model constructed in this study had an independent predictive ability to distinguish patients with a high risk of death from those with a low-risk score, and it can be used as a practical and reliable prognostic tool for BRCA. |
format | Online Article Text |
id | pubmed-9898304 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-98983042023-02-05 Identification and validation of a five-gene prognostic signature based on bioinformatics analyses in breast cancer Du, Xin-jie Yang, Xian-rong Wang, Qi-cai Lin, Guo-liang Li, Peng-fei Zhang, Wei-feng Heliyon Research Article BACKGROUND: This study aimed to identify prognostic signatures to predict the prognosis of breast cancer (BRCA) patients based on a series of comprehensive analyses of gene expression data. METHODS: The RNA-sequencing expression data and corresponding BRCA patient clinical data were collected from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets. Firstly, the differently expressed genes (DEGs) related to prognosis between tumor tissues and normal tissues were ascertained by performing R package “limma”. Secondly, the DEGs were used to construct a polygenic risk scoring model by the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator Cox regression (Lasso-cox) analysis method. Thirdly, survival analysis was performed to investigate the risk score values in the TCGA cohort. And the enrichment analysis, immune cell infiltration levels analysis, and protein-protein internet (PPI) analysis were performed. Simultaneously, the GEO cohort was used to validate the model. Lastly, we constructed a nomogram to explore the influence of polygenic risk score and other clinical factors on the survival probability of patients with BRCA. RESULTS: A total of 1000 DEGs including 396 upregulated genes and 604 downregulated genes were identified from the TCGA-BRCA dataset. We obtained 5 prognosis-related genes, as the key biomarkers by Lasso-cox analysis (FBXL19, HAGHL, PHKG2, PKMYT1, and TXNDC17), all of which were significantly upregulated in breast tumors. The prognostic prediction of the 5 genes model was great in training and validation cohorts. Moreover, the high-risk group had a poorer prognosis. The Cox regression analysis showed that the comprehensive risk score for 5 genes was an independent prognosis factor. CONCLUSION: The 5 genes risk model constructed in this study had an independent predictive ability to distinguish patients with a high risk of death from those with a low-risk score, and it can be used as a practical and reliable prognostic tool for BRCA. Elsevier 2023-01-27 /pmc/articles/PMC9898304/ /pubmed/36747547 http://dx.doi.org/10.1016/j.heliyon.2023.e13185 Text en © 2023 The Authors. Published by Elsevier Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Du, Xin-jie Yang, Xian-rong Wang, Qi-cai Lin, Guo-liang Li, Peng-fei Zhang, Wei-feng Identification and validation of a five-gene prognostic signature based on bioinformatics analyses in breast cancer |
title | Identification and validation of a five-gene prognostic signature based on bioinformatics analyses in breast cancer |
title_full | Identification and validation of a five-gene prognostic signature based on bioinformatics analyses in breast cancer |
title_fullStr | Identification and validation of a five-gene prognostic signature based on bioinformatics analyses in breast cancer |
title_full_unstemmed | Identification and validation of a five-gene prognostic signature based on bioinformatics analyses in breast cancer |
title_short | Identification and validation of a five-gene prognostic signature based on bioinformatics analyses in breast cancer |
title_sort | identification and validation of a five-gene prognostic signature based on bioinformatics analyses in breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9898304/ https://www.ncbi.nlm.nih.gov/pubmed/36747547 http://dx.doi.org/10.1016/j.heliyon.2023.e13185 |
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