Adipogenesis in triple-negative breast cancer is associated with unfavorable tumor immune microenvironment and with worse survival

Abstract Cancer-associated adipocytes are known to cause inflammation; however, the role of adipogenesis, the formation of adipocytes, in breast cancer is unclear. We hypothesized that intra-tumoral adipogenesis reflects a different cancer biology than abundance of intra-tumoral adipocytes. The Mole...

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Autores principales:	Masanori Oshi, Yoshihisa Tokumaru, Fernando A. Angarita, Lan Lee, Li Yan, Ryusei Matsuyama, Itaru Endo, Kazuaki Takabe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8e8e578ee3e7418aa94b0630ea1d77e0
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spelling	oai:doaj.org-article:8e8e578ee3e7418aa94b0630ea1d77e02021-12-02T17:24:00ZAdipogenesis in triple-negative breast cancer is associated with unfavorable tumor immune microenvironment and with worse survival10.1038/s41598-021-91897-72045-2322https://doaj.org/article/8e8e578ee3e7418aa94b0630ea1d77e02021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91897-7https://doaj.org/toc/2045-2322Abstract Cancer-associated adipocytes are known to cause inflammation; however, the role of adipogenesis, the formation of adipocytes, in breast cancer is unclear. We hypothesized that intra-tumoral adipogenesis reflects a different cancer biology than abundance of intra-tumoral adipocytes. The Molecular Signatures Database Hallmark adipogenesis gene set of gene set variant analysis was used to quantify adipogenesis. Total of 5,098 breast cancer patients in multiple cohorts (training; GSE96058 (n = 3273), validation; TCGA (n = 1069), treatment response; GSE25066 (n = 508) and GSE20194 (n = 248)) were analyzed. Adipogenesis did not correlate with abundance of adipocytes. Adipogenesis was significantly lower in triple negative breast cancer (TNBC). Elevated adipogenesis was significantly associated with worse survival in TNBC, but not in the other subtypes. High adipogenesis TNBC was significantly associated with low homologous recombination deficiency, but not with mutation load. High adipogenesis TNBC enriched metabolism-related gene sets, but neither of cell proliferation- nor inflammation-related gene sets, which were enriched to adipocytes. High adipogenesis TNBC was infiltrated with low CD8+ T cells and high M2 macrophages. Although adipogenesis was not associated with neoadjuvant chemotherapy response, high adipogenesis TNBC was significantly associated with low expression of PD-L1 and PD-L2 genes, and immune checkpoint molecules index. In conclusion, adipogenesis in TNBC was associated with cancer metabolism and unfavorable tumor immune microenvironment, which is different from abundance of adipocytes.Masanori OshiYoshihisa TokumaruFernando A. AngaritaLan LeeLi YanRyusei MatsuyamaItaru EndoKazuaki TakabeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Masanori Oshi Yoshihisa Tokumaru Fernando A. Angarita Lan Lee Li Yan Ryusei Matsuyama Itaru Endo Kazuaki Takabe Adipogenesis in triple-negative breast cancer is associated with unfavorable tumor immune microenvironment and with worse survival
description	Abstract Cancer-associated adipocytes are known to cause inflammation; however, the role of adipogenesis, the formation of adipocytes, in breast cancer is unclear. We hypothesized that intra-tumoral adipogenesis reflects a different cancer biology than abundance of intra-tumoral adipocytes. The Molecular Signatures Database Hallmark adipogenesis gene set of gene set variant analysis was used to quantify adipogenesis. Total of 5,098 breast cancer patients in multiple cohorts (training; GSE96058 (n = 3273), validation; TCGA (n = 1069), treatment response; GSE25066 (n = 508) and GSE20194 (n = 248)) were analyzed. Adipogenesis did not correlate with abundance of adipocytes. Adipogenesis was significantly lower in triple negative breast cancer (TNBC). Elevated adipogenesis was significantly associated with worse survival in TNBC, but not in the other subtypes. High adipogenesis TNBC was significantly associated with low homologous recombination deficiency, but not with mutation load. High adipogenesis TNBC enriched metabolism-related gene sets, but neither of cell proliferation- nor inflammation-related gene sets, which were enriched to adipocytes. High adipogenesis TNBC was infiltrated with low CD8+ T cells and high M2 macrophages. Although adipogenesis was not associated with neoadjuvant chemotherapy response, high adipogenesis TNBC was significantly associated with low expression of PD-L1 and PD-L2 genes, and immune checkpoint molecules index. In conclusion, adipogenesis in TNBC was associated with cancer metabolism and unfavorable tumor immune microenvironment, which is different from abundance of adipocytes.
format	article
author	Masanori Oshi Yoshihisa Tokumaru Fernando A. Angarita Lan Lee Li Yan Ryusei Matsuyama Itaru Endo Kazuaki Takabe
author_facet	Masanori Oshi Yoshihisa Tokumaru Fernando A. Angarita Lan Lee Li Yan Ryusei Matsuyama Itaru Endo Kazuaki Takabe
author_sort	Masanori Oshi
title	Adipogenesis in triple-negative breast cancer is associated with unfavorable tumor immune microenvironment and with worse survival
title_short	Adipogenesis in triple-negative breast cancer is associated with unfavorable tumor immune microenvironment and with worse survival
title_full	Adipogenesis in triple-negative breast cancer is associated with unfavorable tumor immune microenvironment and with worse survival
title_fullStr	Adipogenesis in triple-negative breast cancer is associated with unfavorable tumor immune microenvironment and with worse survival
title_full_unstemmed	Adipogenesis in triple-negative breast cancer is associated with unfavorable tumor immune microenvironment and with worse survival
title_sort	adipogenesis in triple-negative breast cancer is associated with unfavorable tumor immune microenvironment and with worse survival
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8e8e578ee3e7418aa94b0630ea1d77e0
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Adipogenesis in triple-negative breast cancer is associated with unfavorable tumor immune microenvironment and with worse survival

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