Identification of gastric cancer subtypes based on pathway clustering

Abstract Gastric cancer (GC) is highly heterogeneous in the stromal and immune microenvironment, genome instability (GI), and oncogenic signatures. However, a classification of GC by combining these features remains lacking. Using the consensus clustering algorithm, we clustered GCs based on the act...

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Autores principales:	Lin Li, Xiaosheng Wang
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/fd1f45e026054cc4b4b226902e92a0c1
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spelling	oai:doaj.org-article:fd1f45e026054cc4b4b226902e92a0c12021-12-02T18:26:00ZIdentification of gastric cancer subtypes based on pathway clustering10.1038/s41698-021-00186-z2397-768Xhttps://doaj.org/article/fd1f45e026054cc4b4b226902e92a0c12021-06-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00186-zhttps://doaj.org/toc/2397-768XAbstract Gastric cancer (GC) is highly heterogeneous in the stromal and immune microenvironment, genome instability (GI), and oncogenic signatures. However, a classification of GC by combining these features remains lacking. Using the consensus clustering algorithm, we clustered GCs based on the activities of 15 pathways associated with immune, DNA repair, oncogenic, and stromal signatures in three GC datasets. We identified three GC subtypes: immunity-deprived (ImD), stroma-enriched (StE), and immunity-enriched (ImE). ImD showed low immune infiltration, high DNA damage repair activity, high tumor aneuploidy level, high intratumor heterogeneity (ITH), and frequent TP53 mutations. StE displayed high stromal signatures, low DNA damage repair activity, genomic stability, low ITH, and poor prognosis. ImE had strong immune infiltration, high DNA damage repair activity, high tumor mutation burden, prevalence of microsatellite instability, frequent ARID1A mutations, elevated PD-L1 expression, and favorable prognosis. Based on the expression levels of four genes (TAP2, SERPINB5, LTBP1, and LAMC1) in immune, DNA repair, oncogenic, and stromal pathways, we developed a prognostic model (IDOScore). The IDOScore was an adverse prognostic factor and correlated inversely with immunotherapy response in cancer. Our identification of new GC subtypes provides novel insights into tumor biology and has potential clinical implications for the management of GCs.Lin LiXiaosheng WangNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-17 (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 Lin Li Xiaosheng Wang Identification of gastric cancer subtypes based on pathway clustering
description	Abstract Gastric cancer (GC) is highly heterogeneous in the stromal and immune microenvironment, genome instability (GI), and oncogenic signatures. However, a classification of GC by combining these features remains lacking. Using the consensus clustering algorithm, we clustered GCs based on the activities of 15 pathways associated with immune, DNA repair, oncogenic, and stromal signatures in three GC datasets. We identified three GC subtypes: immunity-deprived (ImD), stroma-enriched (StE), and immunity-enriched (ImE). ImD showed low immune infiltration, high DNA damage repair activity, high tumor aneuploidy level, high intratumor heterogeneity (ITH), and frequent TP53 mutations. StE displayed high stromal signatures, low DNA damage repair activity, genomic stability, low ITH, and poor prognosis. ImE had strong immune infiltration, high DNA damage repair activity, high tumor mutation burden, prevalence of microsatellite instability, frequent ARID1A mutations, elevated PD-L1 expression, and favorable prognosis. Based on the expression levels of four genes (TAP2, SERPINB5, LTBP1, and LAMC1) in immune, DNA repair, oncogenic, and stromal pathways, we developed a prognostic model (IDOScore). The IDOScore was an adverse prognostic factor and correlated inversely with immunotherapy response in cancer. Our identification of new GC subtypes provides novel insights into tumor biology and has potential clinical implications for the management of GCs.
format	article
author	Lin Li Xiaosheng Wang
author_facet	Lin Li Xiaosheng Wang
author_sort	Lin Li
title	Identification of gastric cancer subtypes based on pathway clustering
title_short	Identification of gastric cancer subtypes based on pathway clustering
title_full	Identification of gastric cancer subtypes based on pathway clustering
title_fullStr	Identification of gastric cancer subtypes based on pathway clustering
title_full_unstemmed	Identification of gastric cancer subtypes based on pathway clustering
title_sort	identification of gastric cancer subtypes based on pathway clustering
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fd1f45e026054cc4b4b226902e92a0c1
work_keys_str_mv	AT linli identificationofgastriccancersubtypesbasedonpathwayclustering AT xiaoshengwang identificationofgastriccancersubtypesbasedonpathwayclustering
_version_	1718378075847131136

Identification of gastric cancer subtypes based on pathway clustering

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