Biologically Aggressive Phenotype and Anti-cancer Immunity Counterbalance in Breast Cancer with High Mutation Rate

Abstract While cancer cells gain aggressiveness by mutations, abundant mutations release neoantigens, attracting anti-cancer immune cells. We hypothesized that in breast cancer (BC), where mutation is less common, tumors with high mutation rates demonstrate aggressive phenotypes and attract immune c...

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Autores principales:	Hideo Takahashi, Mariko Asaoka, Li Yan, Omar M. Rashid, Masanori Oshi, Takashi Ishikawa, Masayuki Nagahashi, Kazuaki Takabe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7da8c6f6d26c4ed3a1ec4b0f1f4f5d48
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spelling	oai:doaj.org-article:7da8c6f6d26c4ed3a1ec4b0f1f4f5d482021-12-02T14:06:51ZBiologically Aggressive Phenotype and Anti-cancer Immunity Counterbalance in Breast Cancer with High Mutation Rate10.1038/s41598-020-58995-42045-2322https://doaj.org/article/7da8c6f6d26c4ed3a1ec4b0f1f4f5d482020-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-58995-4https://doaj.org/toc/2045-2322Abstract While cancer cells gain aggressiveness by mutations, abundant mutations release neoantigens, attracting anti-cancer immune cells. We hypothesized that in breast cancer (BC), where mutation is less common, tumors with high mutation rates demonstrate aggressive phenotypes and attract immune cells simultaneously. High mutation rates were defined as the top 10% of the mutation rate, utilizing TCGA and METABRIC transcriptomic data. Mutation rate did not impact survival although high mutation BCs were associated with aggressive clinical features, such as more frequent in ER-negative tumors (p < 0.01), in triple-negative subtype (p = 0.03), and increased MKI-67 mRNA expression (p < 0.01) in both cohorts. Tumors with high mutation rates were associated with APOBEC3B and homologous recombination deficiency, increasing neoantigen loads (all p < 0.01). Cell proliferation and immune activity pathways were enriched in BCs with high mutation rates. Furthermore, there were higher lymphocytes and M1 macrophage infiltration in high mutation BCs. Additionally, T-cell receptor diversity, cytolytic activity score (CYT), and T-cell exhaustion marker expression were significantly elevated in BCs with high mutation rates (all p < 0.01), indicating strong immunogenicity. In conclusion, enhanced immunity due to neoantigens can be one of possible forces to counterbalance aggressiveness of a high mutation rate, resulting in similar survival rates to low mutation BCs.Hideo TakahashiMariko AsaokaLi YanOmar M. RashidMasanori OshiTakashi IshikawaMasayuki NagahashiKazuaki TakabeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hideo Takahashi Mariko Asaoka Li Yan Omar M. Rashid Masanori Oshi Takashi Ishikawa Masayuki Nagahashi Kazuaki Takabe Biologically Aggressive Phenotype and Anti-cancer Immunity Counterbalance in Breast Cancer with High Mutation Rate
description	Abstract While cancer cells gain aggressiveness by mutations, abundant mutations release neoantigens, attracting anti-cancer immune cells. We hypothesized that in breast cancer (BC), where mutation is less common, tumors with high mutation rates demonstrate aggressive phenotypes and attract immune cells simultaneously. High mutation rates were defined as the top 10% of the mutation rate, utilizing TCGA and METABRIC transcriptomic data. Mutation rate did not impact survival although high mutation BCs were associated with aggressive clinical features, such as more frequent in ER-negative tumors (p < 0.01), in triple-negative subtype (p = 0.03), and increased MKI-67 mRNA expression (p < 0.01) in both cohorts. Tumors with high mutation rates were associated with APOBEC3B and homologous recombination deficiency, increasing neoantigen loads (all p < 0.01). Cell proliferation and immune activity pathways were enriched in BCs with high mutation rates. Furthermore, there were higher lymphocytes and M1 macrophage infiltration in high mutation BCs. Additionally, T-cell receptor diversity, cytolytic activity score (CYT), and T-cell exhaustion marker expression were significantly elevated in BCs with high mutation rates (all p < 0.01), indicating strong immunogenicity. In conclusion, enhanced immunity due to neoantigens can be one of possible forces to counterbalance aggressiveness of a high mutation rate, resulting in similar survival rates to low mutation BCs.
format	article
author	Hideo Takahashi Mariko Asaoka Li Yan Omar M. Rashid Masanori Oshi Takashi Ishikawa Masayuki Nagahashi Kazuaki Takabe
author_facet	Hideo Takahashi Mariko Asaoka Li Yan Omar M. Rashid Masanori Oshi Takashi Ishikawa Masayuki Nagahashi Kazuaki Takabe
author_sort	Hideo Takahashi
title	Biologically Aggressive Phenotype and Anti-cancer Immunity Counterbalance in Breast Cancer with High Mutation Rate
title_short	Biologically Aggressive Phenotype and Anti-cancer Immunity Counterbalance in Breast Cancer with High Mutation Rate
title_full	Biologically Aggressive Phenotype and Anti-cancer Immunity Counterbalance in Breast Cancer with High Mutation Rate
title_fullStr	Biologically Aggressive Phenotype and Anti-cancer Immunity Counterbalance in Breast Cancer with High Mutation Rate
title_full_unstemmed	Biologically Aggressive Phenotype and Anti-cancer Immunity Counterbalance in Breast Cancer with High Mutation Rate
title_sort	biologically aggressive phenotype and anti-cancer immunity counterbalance in breast cancer with high mutation rate
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/7da8c6f6d26c4ed3a1ec4b0f1f4f5d48
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Biologically Aggressive Phenotype and Anti-cancer Immunity Counterbalance in Breast Cancer with High Mutation Rate

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