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Expression and clinical implications of basic leucine zipper ATF-like transcription factor 2 in breast cancer

BACKGROUND: Basic leucine zipper ATF-like transcription factor 2 (BATF2) has been reported to participate in the occurrence and development of some malignancies. Herein, we aimed to explore the expression pattern and clinical implications of BATF2 in breast cancer (BC). METHODS: We assessed the diff...

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Autores principales: Lin, Yingying, Zhou, Xusheng, Peng, Wei, Wu, Jing, Wu, Xiufeng, Chen, Yan, Cui, Zhaolei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474811/
https://www.ncbi.nlm.nih.gov/pubmed/34565331
http://dx.doi.org/10.1186/s12885-021-08785-6
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author Lin, Yingying
Zhou, Xusheng
Peng, Wei
Wu, Jing
Wu, Xiufeng
Chen, Yan
Cui, Zhaolei
author_facet Lin, Yingying
Zhou, Xusheng
Peng, Wei
Wu, Jing
Wu, Xiufeng
Chen, Yan
Cui, Zhaolei
author_sort Lin, Yingying
collection PubMed
description BACKGROUND: Basic leucine zipper ATF-like transcription factor 2 (BATF2) has been reported to participate in the occurrence and development of some malignancies. Herein, we aimed to explore the expression pattern and clinical implications of BATF2 in breast cancer (BC). METHODS: We assessed the differences in BATF2 mRNA expression between cancerous and noncancerous tissues in BC using GEPIA and UALCAN data and in BATF2 protein expression pattern using Human Protein Atlas (HPA) data. BATF2 co-expression networks were analyzed in Coexpedia. The association between the differentially expressed BATF2 mRNA and BC prognosis was assessed using UALCAN, OSbrca, and GEPIA databases. In external validations, BATF2 protein expression in BC tissues was quantitated using a tissue microarray and immunohistochemistry (IHC) analysis, and BATF2 mRNA expression in serum and serum-derived exosomes of BC patients using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: No difference in the BATF2 mRNA expression level was found between cancerous and noncancerous tissues in BC based on databases. There were low-to-moderate levels of increases in BATF2 protein expressions in BC cases from the HPA cohort. BATF2 mRNA expression was negatively correlated with androgen receptor (AR) and positively correlated with BRCA2 DNA repair associated (BRCA2), marker of proliferation Ki-67 (Mki67), and tumor protein p53 (TP53) expressions. Generally, BATF2 mRNA exhibited a non-significant association with BC prognosis; yet the subgroup analyses showed that triple-negative breast cancer (TNBC) patients with high BATF2 mRNA expressions had a longer overall survival (OS). Our IHC analysis revealed a positive rate of BATF2 protein expression of 46.90%, mainly located in the nucleus of cancer cells in BC, and the OS of BC patients with high BATF2 protein expressions was prolonged. The positive rates of BATF2 mRNA expressions in the serum and exosomes were 45.00 and 41.67%, respectively. Besides, the AUCs of serum and exosomal BATF2 mRNA for BC diagnosis were 0.8929 and 0.8869, respectively. CONCLUSIONS: BC patients exhibit low-to-moderate expressions in BATF2 mRNA expression levels in cancerous tissues. The high BATF2 protein expression can be a potential indicator of a better BC prognosis. Serum and exosomal BATF2 mRNA levels also serve as promising noninvasive biomarkers for BC diagnosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08785-6.
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spelling pubmed-84748112021-09-28 Expression and clinical implications of basic leucine zipper ATF-like transcription factor 2 in breast cancer Lin, Yingying Zhou, Xusheng Peng, Wei Wu, Jing Wu, Xiufeng Chen, Yan Cui, Zhaolei BMC Cancer Research Article BACKGROUND: Basic leucine zipper ATF-like transcription factor 2 (BATF2) has been reported to participate in the occurrence and development of some malignancies. Herein, we aimed to explore the expression pattern and clinical implications of BATF2 in breast cancer (BC). METHODS: We assessed the differences in BATF2 mRNA expression between cancerous and noncancerous tissues in BC using GEPIA and UALCAN data and in BATF2 protein expression pattern using Human Protein Atlas (HPA) data. BATF2 co-expression networks were analyzed in Coexpedia. The association between the differentially expressed BATF2 mRNA and BC prognosis was assessed using UALCAN, OSbrca, and GEPIA databases. In external validations, BATF2 protein expression in BC tissues was quantitated using a tissue microarray and immunohistochemistry (IHC) analysis, and BATF2 mRNA expression in serum and serum-derived exosomes of BC patients using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: No difference in the BATF2 mRNA expression level was found between cancerous and noncancerous tissues in BC based on databases. There were low-to-moderate levels of increases in BATF2 protein expressions in BC cases from the HPA cohort. BATF2 mRNA expression was negatively correlated with androgen receptor (AR) and positively correlated with BRCA2 DNA repair associated (BRCA2), marker of proliferation Ki-67 (Mki67), and tumor protein p53 (TP53) expressions. Generally, BATF2 mRNA exhibited a non-significant association with BC prognosis; yet the subgroup analyses showed that triple-negative breast cancer (TNBC) patients with high BATF2 mRNA expressions had a longer overall survival (OS). Our IHC analysis revealed a positive rate of BATF2 protein expression of 46.90%, mainly located in the nucleus of cancer cells in BC, and the OS of BC patients with high BATF2 protein expressions was prolonged. The positive rates of BATF2 mRNA expressions in the serum and exosomes were 45.00 and 41.67%, respectively. Besides, the AUCs of serum and exosomal BATF2 mRNA for BC diagnosis were 0.8929 and 0.8869, respectively. CONCLUSIONS: BC patients exhibit low-to-moderate expressions in BATF2 mRNA expression levels in cancerous tissues. The high BATF2 protein expression can be a potential indicator of a better BC prognosis. Serum and exosomal BATF2 mRNA levels also serve as promising noninvasive biomarkers for BC diagnosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08785-6. BioMed Central 2021-09-26 /pmc/articles/PMC8474811/ /pubmed/34565331 http://dx.doi.org/10.1186/s12885-021-08785-6 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 Article
Lin, Yingying
Zhou, Xusheng
Peng, Wei
Wu, Jing
Wu, Xiufeng
Chen, Yan
Cui, Zhaolei
Expression and clinical implications of basic leucine zipper ATF-like transcription factor 2 in breast cancer
title Expression and clinical implications of basic leucine zipper ATF-like transcription factor 2 in breast cancer
title_full Expression and clinical implications of basic leucine zipper ATF-like transcription factor 2 in breast cancer
title_fullStr Expression and clinical implications of basic leucine zipper ATF-like transcription factor 2 in breast cancer
title_full_unstemmed Expression and clinical implications of basic leucine zipper ATF-like transcription factor 2 in breast cancer
title_short Expression and clinical implications of basic leucine zipper ATF-like transcription factor 2 in breast cancer
title_sort expression and clinical implications of basic leucine zipper atf-like transcription factor 2 in breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474811/
https://www.ncbi.nlm.nih.gov/pubmed/34565331
http://dx.doi.org/10.1186/s12885-021-08785-6
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