Identification of immune-related subtypes of colorectal cancer to improve antitumor immunotherapy

Abstract Immunotherapy involving immune checkpoint inhibitors (ICIs) for enhancing immune system activation is promising for tumor management. However, the patients’ responses to ICIs are different. Here, we applied a non-negative matrix factorization algorithm to establish a robust immune molecular...

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Autores principales:	Xiaobo Zheng, Yong Gao, Chune Yu, Guiquan Fan, Pengwu Li, Ming Zhang, Jing Yu, Mingqing Xu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/db8de9deba9d4bffa447c849eff4416b
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spelling	oai:doaj.org-article:db8de9deba9d4bffa447c849eff4416b2021-12-02T17:18:21ZIdentification of immune-related subtypes of colorectal cancer to improve antitumor immunotherapy10.1038/s41598-021-98966-x2045-2322https://doaj.org/article/db8de9deba9d4bffa447c849eff4416b2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98966-xhttps://doaj.org/toc/2045-2322Abstract Immunotherapy involving immune checkpoint inhibitors (ICIs) for enhancing immune system activation is promising for tumor management. However, the patients’ responses to ICIs are different. Here, we applied a non-negative matrix factorization algorithm to establish a robust immune molecular classification system for colorectal cancer (CRC). We obtained data of 1503 CRC patients (training cohort: 488 from The Cancer Genome Atlas; validation cohort: 1015 from the Gene Expression Omnibus). In the training cohort, 42.8% of patients who exhibited significantly higher immunocyte infiltration and enrichment of immune response-associated signatures were subdivided into immune classes. Within the immune class, 53.1% of patients were associated with a worse overall prognosis and belonged to the immune-suppressed subclass, characterized by the activation of stroma-related signatures, genes, immune-suppressive cells, and signaling. The remaining immune class patients belonged to the immune-activated subclass, which was associated with a better prognosis and response to anti-PD-1 therapy. Immune-related subtypes were associated with different copy number alterations, tumor-infiltrating lymphocyte enrichment, PD-1/PD-L1 expression, mutation landscape, and cancer stemness. These results were validated in patients with microsatellite instable CRC. We described a novel immune-related class of CRC, which may be used for selecting candidate patients with CRC for immunotherapy and tailoring optimal immunotherapeutic treatment.Xiaobo ZhengYong GaoChune YuGuiquan FanPengwu LiMing ZhangJing YuMingqing XuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaobo Zheng Yong Gao Chune Yu Guiquan Fan Pengwu Li Ming Zhang Jing Yu Mingqing Xu Identification of immune-related subtypes of colorectal cancer to improve antitumor immunotherapy
description	Abstract Immunotherapy involving immune checkpoint inhibitors (ICIs) for enhancing immune system activation is promising for tumor management. However, the patients’ responses to ICIs are different. Here, we applied a non-negative matrix factorization algorithm to establish a robust immune molecular classification system for colorectal cancer (CRC). We obtained data of 1503 CRC patients (training cohort: 488 from The Cancer Genome Atlas; validation cohort: 1015 from the Gene Expression Omnibus). In the training cohort, 42.8% of patients who exhibited significantly higher immunocyte infiltration and enrichment of immune response-associated signatures were subdivided into immune classes. Within the immune class, 53.1% of patients were associated with a worse overall prognosis and belonged to the immune-suppressed subclass, characterized by the activation of stroma-related signatures, genes, immune-suppressive cells, and signaling. The remaining immune class patients belonged to the immune-activated subclass, which was associated with a better prognosis and response to anti-PD-1 therapy. Immune-related subtypes were associated with different copy number alterations, tumor-infiltrating lymphocyte enrichment, PD-1/PD-L1 expression, mutation landscape, and cancer stemness. These results were validated in patients with microsatellite instable CRC. We described a novel immune-related class of CRC, which may be used for selecting candidate patients with CRC for immunotherapy and tailoring optimal immunotherapeutic treatment.
format	article
author	Xiaobo Zheng Yong Gao Chune Yu Guiquan Fan Pengwu Li Ming Zhang Jing Yu Mingqing Xu
author_facet	Xiaobo Zheng Yong Gao Chune Yu Guiquan Fan Pengwu Li Ming Zhang Jing Yu Mingqing Xu
author_sort	Xiaobo Zheng
title	Identification of immune-related subtypes of colorectal cancer to improve antitumor immunotherapy
title_short	Identification of immune-related subtypes of colorectal cancer to improve antitumor immunotherapy
title_full	Identification of immune-related subtypes of colorectal cancer to improve antitumor immunotherapy
title_fullStr	Identification of immune-related subtypes of colorectal cancer to improve antitumor immunotherapy
title_full_unstemmed	Identification of immune-related subtypes of colorectal cancer to improve antitumor immunotherapy
title_sort	identification of immune-related subtypes of colorectal cancer to improve antitumor immunotherapy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/db8de9deba9d4bffa447c849eff4416b
work_keys_str_mv	AT xiaobozheng identificationofimmunerelatedsubtypesofcolorectalcancertoimproveantitumorimmunotherapy AT yonggao identificationofimmunerelatedsubtypesofcolorectalcancertoimproveantitumorimmunotherapy AT chuneyu identificationofimmunerelatedsubtypesofcolorectalcancertoimproveantitumorimmunotherapy AT guiquanfan identificationofimmunerelatedsubtypesofcolorectalcancertoimproveantitumorimmunotherapy AT pengwuli identificationofimmunerelatedsubtypesofcolorectalcancertoimproveantitumorimmunotherapy AT mingzhang identificationofimmunerelatedsubtypesofcolorectalcancertoimproveantitumorimmunotherapy AT jingyu identificationofimmunerelatedsubtypesofcolorectalcancertoimproveantitumorimmunotherapy AT mingqingxu identificationofimmunerelatedsubtypesofcolorectalcancertoimproveantitumorimmunotherapy
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Identification of immune-related subtypes of colorectal cancer to improve antitumor immunotherapy

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