High prevalence of APOA1/C3/A4/A5 alterations in luminal breast cancers among young women in East Asia

Abstract In East Asia, the breast cancer incidence rate among women aged <50 years has rapidly increased. Emerging tumors are distinctly characterized by a high prevalence of estrogen receptor (ER)–positive/human epidermal growth factor receptor (HER2)–negative cancer. In the present study, we id...

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Autores principales:	Ching-Hung Lin, Ruby Yun-Ju Huang, Tzu-Pin Lu, Kuan-Ting Kuo, Ko-Yun Lo, Ching-Hsuan Chen, I-Chun Chen, Yen-Shen Lu, Eric Y. Chuang, Jean Paul Thiery, Chiun-Sheng Huang, Ann-Lii Cheng
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/639f57b5e1b448d0bef6e0021dda94f1
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spelling	oai:doaj.org-article:639f57b5e1b448d0bef6e0021dda94f12021-12-02T15:39:42ZHigh prevalence of APOA1/C3/A4/A5 alterations in luminal breast cancers among young women in East Asia10.1038/s41523-021-00299-52374-4677https://doaj.org/article/639f57b5e1b448d0bef6e0021dda94f12021-07-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00299-5https://doaj.org/toc/2374-4677Abstract In East Asia, the breast cancer incidence rate among women aged <50 years has rapidly increased. Emerging tumors are distinctly characterized by a high prevalence of estrogen receptor (ER)–positive/human epidermal growth factor receptor (HER2)–negative cancer. In the present study, we identified unique genetic alterations in these emerging tumors. We analyzed gene copy number variations (CNVs) in breast tumors from 120 Taiwanese patients, and obtained public datasets of CNV and gene expression (GE). The data regarding CNV and GE were separately compared between East Asian and Western patients, and the overlapping genes identified in the comparisons were explored to identify the gene–gene interaction networks. In the age <50 years/ER + /HER2– subgroup, tumors of East Asian patients exhibited a higher frequency of copy number loss in APOA1/C3/A4/A5, a lipid-metabolizing gene cluster (33 vs. 10%, P < .001) and lower APOA1/C3/A4/A5 expressions than tumors of Western patients. These copy number loss related– and GE–related results were validated in another Taiwanese cohort and in two GE datasets, respectively. The copy number loss was significantly associated with poor survival among Western patients, but not among East Asian patients. Lower APOA1, APOC3, and APOA5 expressions were associated with higher ESTIMATE immune scores, indicating an abundance of tumor-infiltrating immune cells. In conclusion, APOA1/C3/A4/A5 copy number loss was more prevalent in luminal breast tumors among East Asian women aged <50 years, and its immunomodulatory effect on the tumor microenvironment possibly plays various roles in the tumor biology of East Asian patients.Ching-Hung LinRuby Yun-Ju HuangTzu-Pin LuKuan-Ting KuoKo-Yun LoChing-Hsuan ChenI-Chun ChenYen-Shen LuEric Y. ChuangJean Paul ThieryChiun-Sheng HuangAnn-Lii ChengNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Ching-Hung Lin Ruby Yun-Ju Huang Tzu-Pin Lu Kuan-Ting Kuo Ko-Yun Lo Ching-Hsuan Chen I-Chun Chen Yen-Shen Lu Eric Y. Chuang Jean Paul Thiery Chiun-Sheng Huang Ann-Lii Cheng High prevalence of APOA1/C3/A4/A5 alterations in luminal breast cancers among young women in East Asia
description	Abstract In East Asia, the breast cancer incidence rate among women aged <50 years has rapidly increased. Emerging tumors are distinctly characterized by a high prevalence of estrogen receptor (ER)–positive/human epidermal growth factor receptor (HER2)–negative cancer. In the present study, we identified unique genetic alterations in these emerging tumors. We analyzed gene copy number variations (CNVs) in breast tumors from 120 Taiwanese patients, and obtained public datasets of CNV and gene expression (GE). The data regarding CNV and GE were separately compared between East Asian and Western patients, and the overlapping genes identified in the comparisons were explored to identify the gene–gene interaction networks. In the age <50 years/ER + /HER2– subgroup, tumors of East Asian patients exhibited a higher frequency of copy number loss in APOA1/C3/A4/A5, a lipid-metabolizing gene cluster (33 vs. 10%, P < .001) and lower APOA1/C3/A4/A5 expressions than tumors of Western patients. These copy number loss related– and GE–related results were validated in another Taiwanese cohort and in two GE datasets, respectively. The copy number loss was significantly associated with poor survival among Western patients, but not among East Asian patients. Lower APOA1, APOC3, and APOA5 expressions were associated with higher ESTIMATE immune scores, indicating an abundance of tumor-infiltrating immune cells. In conclusion, APOA1/C3/A4/A5 copy number loss was more prevalent in luminal breast tumors among East Asian women aged <50 years, and its immunomodulatory effect on the tumor microenvironment possibly plays various roles in the tumor biology of East Asian patients.
format	article
author	Ching-Hung Lin Ruby Yun-Ju Huang Tzu-Pin Lu Kuan-Ting Kuo Ko-Yun Lo Ching-Hsuan Chen I-Chun Chen Yen-Shen Lu Eric Y. Chuang Jean Paul Thiery Chiun-Sheng Huang Ann-Lii Cheng
author_facet	Ching-Hung Lin Ruby Yun-Ju Huang Tzu-Pin Lu Kuan-Ting Kuo Ko-Yun Lo Ching-Hsuan Chen I-Chun Chen Yen-Shen Lu Eric Y. Chuang Jean Paul Thiery Chiun-Sheng Huang Ann-Lii Cheng
author_sort	Ching-Hung Lin
title	High prevalence of APOA1/C3/A4/A5 alterations in luminal breast cancers among young women in East Asia
title_short	High prevalence of APOA1/C3/A4/A5 alterations in luminal breast cancers among young women in East Asia
title_full	High prevalence of APOA1/C3/A4/A5 alterations in luminal breast cancers among young women in East Asia
title_fullStr	High prevalence of APOA1/C3/A4/A5 alterations in luminal breast cancers among young women in East Asia
title_full_unstemmed	High prevalence of APOA1/C3/A4/A5 alterations in luminal breast cancers among young women in East Asia
title_sort	high prevalence of apoa1/c3/a4/a5 alterations in luminal breast cancers among young women in east asia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/639f57b5e1b448d0bef6e0021dda94f1
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High prevalence of APOA1/C3/A4/A5 alterations in luminal breast cancers among young women in East Asia

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