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Highly heterogeneous-related genes of triple-negative breast cancer: potential diagnostic and prognostic biomarkers

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype of breast cancer, showing aggressive clinical behaviors and poor outcomes. It urgently needs new therapeutic strategies to improve the prognosis of TNBC. Bioinformatics analyses have been widely used to identify poten...

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Autores principales: Liu, Yiduo, Teng, Linxin, Fu, Shiyi, Wang, Guiyang, Li, Zhengjun, Ding, Chao, Wang, Haodi, Bi, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165798/
https://www.ncbi.nlm.nih.gov/pubmed/34053447
http://dx.doi.org/10.1186/s12885-021-08318-1
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author Liu, Yiduo
Teng, Linxin
Fu, Shiyi
Wang, Guiyang
Li, Zhengjun
Ding, Chao
Wang, Haodi
Bi, Lei
author_facet Liu, Yiduo
Teng, Linxin
Fu, Shiyi
Wang, Guiyang
Li, Zhengjun
Ding, Chao
Wang, Haodi
Bi, Lei
author_sort Liu, Yiduo
collection PubMed
description BACKGROUND: Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype of breast cancer, showing aggressive clinical behaviors and poor outcomes. It urgently needs new therapeutic strategies to improve the prognosis of TNBC. Bioinformatics analyses have been widely used to identify potential biomarkers for facilitating TNBC diagnosis and management. METHODS: We identified potential biomarkers and analyzed their diagnostic and prognostic values using bioinformatics approaches. Including differential expression gene (DEG) analysis, Receiver Operating Characteristic (ROC) curve analysis, functional enrichment analysis, Protein-Protein Interaction (PPI) network construction, survival analysis, multivariate Cox regression analysis, and Non-negative Matrix Factorization (NMF). RESULTS: A total of 105 DEGs were identified between TNBC and other breast cancer subtypes, which were regarded as heterogeneous-related genes. Subsequently, the KEGG enrichment analysis showed that these genes were significantly enriched in ‘cell cycle’ and ‘oocyte meiosis’ related pathways. Four (FAM83B, KITLG, CFD and RBM24) of 105 genes were identified as prognostic signatures in the disease-free interval (DFI) of TNBC patients, as for progression-free interval (PFI), five genes (FAM83B, EXO1, S100B, TYMS and CFD) were obtained. Time-dependent ROC analysis indicated that the multivariate Cox regression models, which were constructed based on these genes, had great predictive performances. Finally, the survival analysis of TNBC subtypes (mesenchymal stem-like [MSL] and mesenchymal [MES]) suggested that FAM83B significantly affected the prognosis of patients. CONCLUSIONS: The multivariate Cox regression models constructed from four heterogeneous-related genes (FAM83B, KITLG, RBM24 and S100B) showed great prediction performance for TNBC patients’ prognostic. Moreover, FAM83B was an important prognostic feature in several TNBC subtypes (MSL and MES). Our findings provided new biomarkers to facilitate the targeted therapies of TNBC and TNBC subtypes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08318-1.
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spelling pubmed-81657982021-06-01 Highly heterogeneous-related genes of triple-negative breast cancer: potential diagnostic and prognostic biomarkers Liu, Yiduo Teng, Linxin Fu, Shiyi Wang, Guiyang Li, Zhengjun Ding, Chao Wang, Haodi Bi, Lei BMC Cancer Research BACKGROUND: Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype of breast cancer, showing aggressive clinical behaviors and poor outcomes. It urgently needs new therapeutic strategies to improve the prognosis of TNBC. Bioinformatics analyses have been widely used to identify potential biomarkers for facilitating TNBC diagnosis and management. METHODS: We identified potential biomarkers and analyzed their diagnostic and prognostic values using bioinformatics approaches. Including differential expression gene (DEG) analysis, Receiver Operating Characteristic (ROC) curve analysis, functional enrichment analysis, Protein-Protein Interaction (PPI) network construction, survival analysis, multivariate Cox regression analysis, and Non-negative Matrix Factorization (NMF). RESULTS: A total of 105 DEGs were identified between TNBC and other breast cancer subtypes, which were regarded as heterogeneous-related genes. Subsequently, the KEGG enrichment analysis showed that these genes were significantly enriched in ‘cell cycle’ and ‘oocyte meiosis’ related pathways. Four (FAM83B, KITLG, CFD and RBM24) of 105 genes were identified as prognostic signatures in the disease-free interval (DFI) of TNBC patients, as for progression-free interval (PFI), five genes (FAM83B, EXO1, S100B, TYMS and CFD) were obtained. Time-dependent ROC analysis indicated that the multivariate Cox regression models, which were constructed based on these genes, had great predictive performances. Finally, the survival analysis of TNBC subtypes (mesenchymal stem-like [MSL] and mesenchymal [MES]) suggested that FAM83B significantly affected the prognosis of patients. CONCLUSIONS: The multivariate Cox regression models constructed from four heterogeneous-related genes (FAM83B, KITLG, RBM24 and S100B) showed great prediction performance for TNBC patients’ prognostic. Moreover, FAM83B was an important prognostic feature in several TNBC subtypes (MSL and MES). Our findings provided new biomarkers to facilitate the targeted therapies of TNBC and TNBC subtypes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08318-1. BioMed Central 2021-05-31 /pmc/articles/PMC8165798/ /pubmed/34053447 http://dx.doi.org/10.1186/s12885-021-08318-1 Text en © The Author(s) 2021 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
Liu, Yiduo
Teng, Linxin
Fu, Shiyi
Wang, Guiyang
Li, Zhengjun
Ding, Chao
Wang, Haodi
Bi, Lei
Highly heterogeneous-related genes of triple-negative breast cancer: potential diagnostic and prognostic biomarkers
title Highly heterogeneous-related genes of triple-negative breast cancer: potential diagnostic and prognostic biomarkers
title_full Highly heterogeneous-related genes of triple-negative breast cancer: potential diagnostic and prognostic biomarkers
title_fullStr Highly heterogeneous-related genes of triple-negative breast cancer: potential diagnostic and prognostic biomarkers
title_full_unstemmed Highly heterogeneous-related genes of triple-negative breast cancer: potential diagnostic and prognostic biomarkers
title_short Highly heterogeneous-related genes of triple-negative breast cancer: potential diagnostic and prognostic biomarkers
title_sort highly heterogeneous-related genes of triple-negative breast cancer: potential diagnostic and prognostic biomarkers
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165798/
https://www.ncbi.nlm.nih.gov/pubmed/34053447
http://dx.doi.org/10.1186/s12885-021-08318-1
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