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A novel disulfidptosis-associated expression pattern in breast cancer based on machine learning
Background: Breast cancer (BC), the leading cause of cancer-related deaths among women, remains a serious threat to human health worldwide. The biological function and prognostic value of disulfidptosis as a novel strategy for BC treatment via induction of cell death remain unknown. Methods: Gene mu...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10343428/ https://www.ncbi.nlm.nih.gov/pubmed/37456667 http://dx.doi.org/10.3389/fgene.2023.1193944 |
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author | Wang, Zhitang Du, Xianqiang Lian, Weibin Chen, Jialin Hong, Chengye Li, Liangqiang Chen, Debo |
author_facet | Wang, Zhitang Du, Xianqiang Lian, Weibin Chen, Jialin Hong, Chengye Li, Liangqiang Chen, Debo |
author_sort | Wang, Zhitang |
collection | PubMed |
description | Background: Breast cancer (BC), the leading cause of cancer-related deaths among women, remains a serious threat to human health worldwide. The biological function and prognostic value of disulfidptosis as a novel strategy for BC treatment via induction of cell death remain unknown. Methods: Gene mutations and copy number variations (CNVs) in 10 disulfidptosis genes were evaluated. Differential expression, prognostic, and univariate Cox analyses were then performed for 10 genes, and BC-specific disulfidptosis-related genes (DRGs) were screened. Unsupervised consensus clustering was used to identify different expression clusters. In addition, we screened the differentially expressed genes (DEGs) among different expression clusters and identified hub genes. Moreover, the expression level of DEGs was detected by RT-qPCR in cellular level. Finally, we used the least absolute shrinkage and selection operator (LASSO) regression algorithm to establish a prognostic feature based on DEGs, and verified the accuracy and sensitivity of its prediction through prognostic analysis and subject operating characteristic curve analysis. The correlation of the signature with the tumor immune microenvironment and tumor stemness was analyzed. Results: Disulfidptosis genes showed significant CNVs. Two clusters were identified based on three DRGs (DNUFS1, LRPPRC, SLC7A11). Cluster A was found to be associated with better survival outcomes(p < 0.05) and higher levels of immune cell infiltration(p < 0.05). A prognostic signature of four disulfidptosis-related DEGs (KIF21A, APOD, ALOX15B, ELOVL2) was developed by LASSO regression analysis. The signature showed a good prediction ability. In addition, the prognostic signature in this study were strongly related to the tumor microenvironment (TME), tumor immune cell infiltration, tumor mutation burden (TMB), tumor stemness, and drug sensitivity. Conclusion: The prognostic signature we constructed based on disulfidptosis-DEGs is a good predictor of prognosis in patients with BC. This prognostic signature is closely related to TME, and its potential correlation provides clues for further studies. |
format | Online Article Text |
id | pubmed-10343428 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103434282023-07-14 A novel disulfidptosis-associated expression pattern in breast cancer based on machine learning Wang, Zhitang Du, Xianqiang Lian, Weibin Chen, Jialin Hong, Chengye Li, Liangqiang Chen, Debo Front Genet Genetics Background: Breast cancer (BC), the leading cause of cancer-related deaths among women, remains a serious threat to human health worldwide. The biological function and prognostic value of disulfidptosis as a novel strategy for BC treatment via induction of cell death remain unknown. Methods: Gene mutations and copy number variations (CNVs) in 10 disulfidptosis genes were evaluated. Differential expression, prognostic, and univariate Cox analyses were then performed for 10 genes, and BC-specific disulfidptosis-related genes (DRGs) were screened. Unsupervised consensus clustering was used to identify different expression clusters. In addition, we screened the differentially expressed genes (DEGs) among different expression clusters and identified hub genes. Moreover, the expression level of DEGs was detected by RT-qPCR in cellular level. Finally, we used the least absolute shrinkage and selection operator (LASSO) regression algorithm to establish a prognostic feature based on DEGs, and verified the accuracy and sensitivity of its prediction through prognostic analysis and subject operating characteristic curve analysis. The correlation of the signature with the tumor immune microenvironment and tumor stemness was analyzed. Results: Disulfidptosis genes showed significant CNVs. Two clusters were identified based on three DRGs (DNUFS1, LRPPRC, SLC7A11). Cluster A was found to be associated with better survival outcomes(p < 0.05) and higher levels of immune cell infiltration(p < 0.05). A prognostic signature of four disulfidptosis-related DEGs (KIF21A, APOD, ALOX15B, ELOVL2) was developed by LASSO regression analysis. The signature showed a good prediction ability. In addition, the prognostic signature in this study were strongly related to the tumor microenvironment (TME), tumor immune cell infiltration, tumor mutation burden (TMB), tumor stemness, and drug sensitivity. Conclusion: The prognostic signature we constructed based on disulfidptosis-DEGs is a good predictor of prognosis in patients with BC. This prognostic signature is closely related to TME, and its potential correlation provides clues for further studies. Frontiers Media S.A. 2023-06-29 /pmc/articles/PMC10343428/ /pubmed/37456667 http://dx.doi.org/10.3389/fgene.2023.1193944 Text en Copyright © 2023 Wang, Du, Lian, Chen, Hong, Li and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Wang, Zhitang Du, Xianqiang Lian, Weibin Chen, Jialin Hong, Chengye Li, Liangqiang Chen, Debo A novel disulfidptosis-associated expression pattern in breast cancer based on machine learning |
title | A novel disulfidptosis-associated expression pattern in breast cancer based on machine learning |
title_full | A novel disulfidptosis-associated expression pattern in breast cancer based on machine learning |
title_fullStr | A novel disulfidptosis-associated expression pattern in breast cancer based on machine learning |
title_full_unstemmed | A novel disulfidptosis-associated expression pattern in breast cancer based on machine learning |
title_short | A novel disulfidptosis-associated expression pattern in breast cancer based on machine learning |
title_sort | novel disulfidptosis-associated expression pattern in breast cancer based on machine learning |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10343428/ https://www.ncbi.nlm.nih.gov/pubmed/37456667 http://dx.doi.org/10.3389/fgene.2023.1193944 |
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