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Lysine lactylation (Kla) might be a novel therapeutic target for breast cancer

BACKGROUND: Histone lysine lactylation (Kla) is a newly identified histone modification, which plays a crucial role in cancer progression. Hence, we determined the prognostic value of Kla in breast cancer (BC). METHODS: We obtained RNA expression profiles of BC from The Cancer Genome Atlas (TCGA), f...

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Autores principales: Deng, Jian, Liao, Xinyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10636881/
https://www.ncbi.nlm.nih.gov/pubmed/37950222
http://dx.doi.org/10.1186/s12920-023-01726-1
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author Deng, Jian
Liao, Xinyi
author_facet Deng, Jian
Liao, Xinyi
author_sort Deng, Jian
collection PubMed
description BACKGROUND: Histone lysine lactylation (Kla) is a newly identified histone modification, which plays a crucial role in cancer progression. Hence, we determined the prognostic value of Kla in breast cancer (BC). METHODS: We obtained RNA expression profiles of BC from The Cancer Genome Atlas (TCGA), following screening out Kla-specific genes. Furthermore, we determined the prognostic value of Kla by constructing a cox model based on Kla-specific genes. Subsequently, we identified expression of lactate accumulation-related genes and prognostic Kla-specific genes through Human Protein Atlas (HPA), and further performed a correlation analysis based on their expression. Meanwhile, we explored the effects of Kla on BC tumor microenvironment (TME), drug therapy and immunotherapy. Moreover, we predicted the pathways influenced by Kla via gene set enrichment analysis (GSEA). RESULTS: A total of 1073 BC samples and 112 normal controls were obtained from TCGA, and 23 tumor samples were removed owing to inadequate clinical information. We identified 257 differentially expressed Kla-specific genes (DEKlaGs) in BC. A cox model involved with CCR7, IGFBP6, NDUFAF6, OVOL1 and SDC1 was established, and risk score could be visualized as an independent biomarker for BC. Meanwhile, Kla was remarkably associated with BC immune microenvironment, drug therapy and immunotherapy. Kla was identified to be related to activation of various BC-related KEGG pathways. CONCLUSION: In conclusion, Kla contributes to drug resistance and undesirable immune responses, and plays a crucial role in BC prognosis, suggesting that Kla was expected to be a new therapeutic target for BC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-023-01726-1.
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spelling pubmed-106368812023-11-11 Lysine lactylation (Kla) might be a novel therapeutic target for breast cancer Deng, Jian Liao, Xinyi BMC Med Genomics Research BACKGROUND: Histone lysine lactylation (Kla) is a newly identified histone modification, which plays a crucial role in cancer progression. Hence, we determined the prognostic value of Kla in breast cancer (BC). METHODS: We obtained RNA expression profiles of BC from The Cancer Genome Atlas (TCGA), following screening out Kla-specific genes. Furthermore, we determined the prognostic value of Kla by constructing a cox model based on Kla-specific genes. Subsequently, we identified expression of lactate accumulation-related genes and prognostic Kla-specific genes through Human Protein Atlas (HPA), and further performed a correlation analysis based on their expression. Meanwhile, we explored the effects of Kla on BC tumor microenvironment (TME), drug therapy and immunotherapy. Moreover, we predicted the pathways influenced by Kla via gene set enrichment analysis (GSEA). RESULTS: A total of 1073 BC samples and 112 normal controls were obtained from TCGA, and 23 tumor samples were removed owing to inadequate clinical information. We identified 257 differentially expressed Kla-specific genes (DEKlaGs) in BC. A cox model involved with CCR7, IGFBP6, NDUFAF6, OVOL1 and SDC1 was established, and risk score could be visualized as an independent biomarker for BC. Meanwhile, Kla was remarkably associated with BC immune microenvironment, drug therapy and immunotherapy. Kla was identified to be related to activation of various BC-related KEGG pathways. CONCLUSION: In conclusion, Kla contributes to drug resistance and undesirable immune responses, and plays a crucial role in BC prognosis, suggesting that Kla was expected to be a new therapeutic target for BC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-023-01726-1. BioMed Central 2023-11-10 /pmc/articles/PMC10636881/ /pubmed/37950222 http://dx.doi.org/10.1186/s12920-023-01726-1 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/) . 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
Deng, Jian
Liao, Xinyi
Lysine lactylation (Kla) might be a novel therapeutic target for breast cancer
title Lysine lactylation (Kla) might be a novel therapeutic target for breast cancer
title_full Lysine lactylation (Kla) might be a novel therapeutic target for breast cancer
title_fullStr Lysine lactylation (Kla) might be a novel therapeutic target for breast cancer
title_full_unstemmed Lysine lactylation (Kla) might be a novel therapeutic target for breast cancer
title_short Lysine lactylation (Kla) might be a novel therapeutic target for breast cancer
title_sort lysine lactylation (kla) might be a novel therapeutic target for breast cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10636881/
https://www.ncbi.nlm.nih.gov/pubmed/37950222
http://dx.doi.org/10.1186/s12920-023-01726-1
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