5mC regulator-mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer

Abstract Background Depicting the heterogeneity and functional characteristics of the tumor microenvironment (TME) is necessary to achieve precision medicine for bladder cancer (BLCA). Although classical molecular subtypes effectively reflect TME heterogeneity and characteristics, their clinical app...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jiao Hu, Belaydi Othmane, Anze Yu, Huihuang Li, Zhiyong Cai, Xu Chen, Wenbiao Ren, Jinbo Chen, Xiongbing Zu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Bladder cancer 5-Methylcytosine Molecular subtype Tumor microenvironment Immune phenotype Immunotherapy Medicine R
Acceso en línea:	https://doaj.org/article/96287c06765c4e27b9cc7331134e41ea
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:96287c06765c4e27b9cc7331134e41ea
record_format	dspace
spelling	oai:doaj.org-article:96287c06765c4e27b9cc7331134e41ea2021-11-28T12:15:17Z5mC regulator-mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer10.1186/s12916-021-02163-61741-7015https://doaj.org/article/96287c06765c4e27b9cc7331134e41ea2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12916-021-02163-6https://doaj.org/toc/1741-7015Abstract Background Depicting the heterogeneity and functional characteristics of the tumor microenvironment (TME) is necessary to achieve precision medicine for bladder cancer (BLCA). Although classical molecular subtypes effectively reflect TME heterogeneity and characteristics, their clinical application is limited by several issues. Methods In this study, we integrated the Xiangya cohort and multiple external BLCA cohorts to develop a novel 5-methylcytosine (5mC) regulator-mediated molecular subtype system and a corresponding quantitative indicator, the 5mC score. Unsupervised clustering was performed to identify novel 5mC regulator-mediated molecular subtypes. The principal component analysis was applied to calculate the 5mC score. Then, we correlated the 5mC clusters (5mC score) with classical molecular subtypes, immunophenotypes, clinical outcomes, and therapeutic opportunities in BLCA. Finally, we performed pancancer analyses on the 5mC score. Results Two 5mC clusters, including 5mC cluster 1 and cluster 2, were identified. These novel 5mC clusters (5mC score) could accurately predict classical molecular subtypes, immunophenotypes, prognosis, and therapeutic opportunities of BLCA. 5mC cluster 1 (high 5mC score) indicated a luminal subtype and noninflamed phenotype, characterized by lower anticancer immunity but better prognosis. Moreover, 5mC cluster 1 (high 5mC score) predicted low sensitivity to cancer immunotherapy, neoadjuvant chemotherapy, and radiotherapy, but high sensitivity to antiangiogenic therapy and targeted therapies, such as blocking the β-catenin, FGFR3, and PPAR-γ pathways. Conclusions The novel 5mC regulator-based subtype system reflects many aspects of BLCA biology and provides new insights into precision medicine in BLCA. Furthermore, the 5mC score may be a generalizable predictor of immunotherapy response and prognosis in pancancers.Jiao HuBelaydi OthmaneAnze YuHuihuang LiZhiyong CaiXu ChenWenbiao RenJinbo ChenXiongbing ZuBMCarticleBladder cancer5-MethylcytosineMolecular subtypeTumor microenvironmentImmune phenotypeImmunotherapyMedicineRENBMC Medicine, Vol 19, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bladder cancer 5-Methylcytosine Molecular subtype Tumor microenvironment Immune phenotype Immunotherapy Medicine R
spellingShingle	Bladder cancer 5-Methylcytosine Molecular subtype Tumor microenvironment Immune phenotype Immunotherapy Medicine R Jiao Hu Belaydi Othmane Anze Yu Huihuang Li Zhiyong Cai Xu Chen Wenbiao Ren Jinbo Chen Xiongbing Zu 5mC regulator-mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer
description	Abstract Background Depicting the heterogeneity and functional characteristics of the tumor microenvironment (TME) is necessary to achieve precision medicine for bladder cancer (BLCA). Although classical molecular subtypes effectively reflect TME heterogeneity and characteristics, their clinical application is limited by several issues. Methods In this study, we integrated the Xiangya cohort and multiple external BLCA cohorts to develop a novel 5-methylcytosine (5mC) regulator-mediated molecular subtype system and a corresponding quantitative indicator, the 5mC score. Unsupervised clustering was performed to identify novel 5mC regulator-mediated molecular subtypes. The principal component analysis was applied to calculate the 5mC score. Then, we correlated the 5mC clusters (5mC score) with classical molecular subtypes, immunophenotypes, clinical outcomes, and therapeutic opportunities in BLCA. Finally, we performed pancancer analyses on the 5mC score. Results Two 5mC clusters, including 5mC cluster 1 and cluster 2, were identified. These novel 5mC clusters (5mC score) could accurately predict classical molecular subtypes, immunophenotypes, prognosis, and therapeutic opportunities of BLCA. 5mC cluster 1 (high 5mC score) indicated a luminal subtype and noninflamed phenotype, characterized by lower anticancer immunity but better prognosis. Moreover, 5mC cluster 1 (high 5mC score) predicted low sensitivity to cancer immunotherapy, neoadjuvant chemotherapy, and radiotherapy, but high sensitivity to antiangiogenic therapy and targeted therapies, such as blocking the β-catenin, FGFR3, and PPAR-γ pathways. Conclusions The novel 5mC regulator-based subtype system reflects many aspects of BLCA biology and provides new insights into precision medicine in BLCA. Furthermore, the 5mC score may be a generalizable predictor of immunotherapy response and prognosis in pancancers.
format	article
author	Jiao Hu Belaydi Othmane Anze Yu Huihuang Li Zhiyong Cai Xu Chen Wenbiao Ren Jinbo Chen Xiongbing Zu
author_facet	Jiao Hu Belaydi Othmane Anze Yu Huihuang Li Zhiyong Cai Xu Chen Wenbiao Ren Jinbo Chen Xiongbing Zu
author_sort	Jiao Hu
title	5mC regulator-mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer
title_short	5mC regulator-mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer
title_full	5mC regulator-mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer
title_fullStr	5mC regulator-mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer
title_full_unstemmed	5mC regulator-mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer
title_sort	5mc regulator-mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer
publisher	BMC
publishDate	2021
url	https://doaj.org/article/96287c06765c4e27b9cc7331134e41ea
work_keys_str_mv	AT jiaohu 5mcregulatormediatedmolecularsubtypesdepictthehallmarksofthetumormicroenvironmentandguideprecisionmedicineinbladdercancer AT belaydiothmane 5mcregulatormediatedmolecularsubtypesdepictthehallmarksofthetumormicroenvironmentandguideprecisionmedicineinbladdercancer AT anzeyu 5mcregulatormediatedmolecularsubtypesdepictthehallmarksofthetumormicroenvironmentandguideprecisionmedicineinbladdercancer AT huihuangli 5mcregulatormediatedmolecularsubtypesdepictthehallmarksofthetumormicroenvironmentandguideprecisionmedicineinbladdercancer AT zhiyongcai 5mcregulatormediatedmolecularsubtypesdepictthehallmarksofthetumormicroenvironmentandguideprecisionmedicineinbladdercancer AT xuchen 5mcregulatormediatedmolecularsubtypesdepictthehallmarksofthetumormicroenvironmentandguideprecisionmedicineinbladdercancer AT wenbiaoren 5mcregulatormediatedmolecularsubtypesdepictthehallmarksofthetumormicroenvironmentandguideprecisionmedicineinbladdercancer AT jinbochen 5mcregulatormediatedmolecularsubtypesdepictthehallmarksofthetumormicroenvironmentandguideprecisionmedicineinbladdercancer AT xiongbingzu 5mcregulatormediatedmolecularsubtypesdepictthehallmarksofthetumormicroenvironmentandguideprecisionmedicineinbladdercancer
_version_	1718408090895777792

5mC regulator-mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer

Ejemplares similares