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Stemness signature and targeted therapeutic drugs identification for Triple Negative Breast Cancer

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and carries the worst prognosis, characterized by the lack of progesterone, estrogen, and HER2 gene expression. This study aimed to analyze cancer stemness-related gene signature to determine patients’ risk stratifi...

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Autores principales: Gul, Samina, Pang, Jianyu, Yuan, Hongjun, Chen, Yongzhi, yu, Qian, Wang, Hui, Tang, Wenru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662149/
https://www.ncbi.nlm.nih.gov/pubmed/37985782
http://dx.doi.org/10.1038/s41597-023-02709-8
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author Gul, Samina
Pang, Jianyu
Yuan, Hongjun
Chen, Yongzhi
yu, Qian
Wang, Hui
Tang, Wenru
author_facet Gul, Samina
Pang, Jianyu
Yuan, Hongjun
Chen, Yongzhi
yu, Qian
Wang, Hui
Tang, Wenru
author_sort Gul, Samina
collection PubMed
description Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and carries the worst prognosis, characterized by the lack of progesterone, estrogen, and HER2 gene expression. This study aimed to analyze cancer stemness-related gene signature to determine patients’ risk stratification and prognosis feature with TNBC. Here one-class logistic regression (OCLR) algorithm was applied to compute the stemness index of TNBC patients. Cox and LASSO regression analysis was performed on stemness-index related genes to establish 16 genes-based prognostic signature, and their predictive performance was verified in TCGA and METABERIC merged data cohort. We diagnosed the expression level of prognostic genes signature in the tumor immune microenvironment, analyzed the TNBC scRNA-seq GSE176078 dataset, and further validated the expression level of prognostic genes using the HPA database. Finally, the small molecular compounds targeted at the anti-tumor effect of predictive genes were screened by molecular docking; this novel stemness-based prognostic genes signature study could facilitate the prognosis of patients with TNBC and thus provide a feasible therapeutic target for TNBC.
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spelling pubmed-106621492023-11-20 Stemness signature and targeted therapeutic drugs identification for Triple Negative Breast Cancer Gul, Samina Pang, Jianyu Yuan, Hongjun Chen, Yongzhi yu, Qian Wang, Hui Tang, Wenru Sci Data Analysis Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and carries the worst prognosis, characterized by the lack of progesterone, estrogen, and HER2 gene expression. This study aimed to analyze cancer stemness-related gene signature to determine patients’ risk stratification and prognosis feature with TNBC. Here one-class logistic regression (OCLR) algorithm was applied to compute the stemness index of TNBC patients. Cox and LASSO regression analysis was performed on stemness-index related genes to establish 16 genes-based prognostic signature, and their predictive performance was verified in TCGA and METABERIC merged data cohort. We diagnosed the expression level of prognostic genes signature in the tumor immune microenvironment, analyzed the TNBC scRNA-seq GSE176078 dataset, and further validated the expression level of prognostic genes using the HPA database. Finally, the small molecular compounds targeted at the anti-tumor effect of predictive genes were screened by molecular docking; this novel stemness-based prognostic genes signature study could facilitate the prognosis of patients with TNBC and thus provide a feasible therapeutic target for TNBC. Nature Publishing Group UK 2023-11-20 /pmc/articles/PMC10662149/ /pubmed/37985782 http://dx.doi.org/10.1038/s41597-023-02709-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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/) .
spellingShingle Analysis
Gul, Samina
Pang, Jianyu
Yuan, Hongjun
Chen, Yongzhi
yu, Qian
Wang, Hui
Tang, Wenru
Stemness signature and targeted therapeutic drugs identification for Triple Negative Breast Cancer
title Stemness signature and targeted therapeutic drugs identification for Triple Negative Breast Cancer
title_full Stemness signature and targeted therapeutic drugs identification for Triple Negative Breast Cancer
title_fullStr Stemness signature and targeted therapeutic drugs identification for Triple Negative Breast Cancer
title_full_unstemmed Stemness signature and targeted therapeutic drugs identification for Triple Negative Breast Cancer
title_short Stemness signature and targeted therapeutic drugs identification for Triple Negative Breast Cancer
title_sort stemness signature and targeted therapeutic drugs identification for triple negative breast cancer
topic Analysis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662149/
https://www.ncbi.nlm.nih.gov/pubmed/37985782
http://dx.doi.org/10.1038/s41597-023-02709-8
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