DNA Methylation Modification Map to Predict Tumor Molecular Subtypes and Efficacy of Immunotherapy in Bladder Cancer
Background: Considering the heterogeneity and complexity of epigenetic regulation in bladder cancer, the underlying mechanisms of global DNA methylation modification in the immune microenvironment must be investigated to predict the prognosis outcomes and clinical response to immunotherapy.Methods:...
Guardado en:
| Autores principales: | , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/227e965f12f74acab84b3886153e2f1c |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:227e965f12f74acab84b3886153e2f1c |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:227e965f12f74acab84b3886153e2f1c2021-12-03T06:57:33ZDNA Methylation Modification Map to Predict Tumor Molecular Subtypes and Efficacy of Immunotherapy in Bladder Cancer2296-634X10.3389/fcell.2021.760369https://doaj.org/article/227e965f12f74acab84b3886153e2f1c2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.760369/fullhttps://doaj.org/toc/2296-634XBackground: Considering the heterogeneity and complexity of epigenetic regulation in bladder cancer, the underlying mechanisms of global DNA methylation modification in the immune microenvironment must be investigated to predict the prognosis outcomes and clinical response to immunotherapy.Methods: We systematically assessed the DNA methylation modes of 985 integrated bladder cancer samples with the unsupervised clustering algorithm. Subsequently, these DNA methylation modes were analyzed for their correlations with features of the immune microenvironment. The principal analysis algorithm was performed to calculate the DMRscores of each samples for qualification analysis.Findings: Three DNA methylation modes were revealed among 985 bladder cancer samples, and these modes are related to diverse clinical outcomes and several immune microenvironment phenotypes, e.g., immune-desert, immune-inflamed, and immune-excluded ones. Then patients were classified into high- and low-DMRscore subgroups according to the DMRscore, which was calculated based on the expression of DNA methylation related genes (DMRGs). Patients with the low-DMRscore subgroup presented a prominent survival advantage that was significantly correlated to the immune-inflamed phenotype. Further analysis revealed that patients with low DMRscores exhibited less TP53 wild mutation, lower cancer stage and molecular subtypes were mainly papillary subtypes. In addition, an independent immunotherapy cohort confirmed that DMRscore could serve as a signature to predict prognosis outcomes and immune responses.Conclusion: Global DNA methylation modes can be used to predict the immunophenotypes, aggressiveness, and immune responses of bladder cancer. DNA methylation status assessments will strengthen our insights into the features of the immune microenvironment and promote the development of more effective treatment strategies.Fangdie YeFangdie YeYingchun LiangYingchun LiangJimeng HuJimeng HuYun HuYun HuYufei LiuYufei LiuZhang ChengZhang ChengYuxi OuYuxi OuChenyang XuChenyang XuHaowen JiangHaowen JiangHaowen JiangFrontiers Media S.A.articlebladder cancerDNA methylation regulatorsimmunotherapyprognostic modeltumor microenvironmentBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
bladder cancer DNA methylation regulators immunotherapy prognostic model tumor microenvironment Biology (General) QH301-705.5 |
| spellingShingle |
bladder cancer DNA methylation regulators immunotherapy prognostic model tumor microenvironment Biology (General) QH301-705.5 Fangdie Ye Fangdie Ye Yingchun Liang Yingchun Liang Jimeng Hu Jimeng Hu Yun Hu Yun Hu Yufei Liu Yufei Liu Zhang Cheng Zhang Cheng Yuxi Ou Yuxi Ou Chenyang Xu Chenyang Xu Haowen Jiang Haowen Jiang Haowen Jiang DNA Methylation Modification Map to Predict Tumor Molecular Subtypes and Efficacy of Immunotherapy in Bladder Cancer |
| description |
Background: Considering the heterogeneity and complexity of epigenetic regulation in bladder cancer, the underlying mechanisms of global DNA methylation modification in the immune microenvironment must be investigated to predict the prognosis outcomes and clinical response to immunotherapy.Methods: We systematically assessed the DNA methylation modes of 985 integrated bladder cancer samples with the unsupervised clustering algorithm. Subsequently, these DNA methylation modes were analyzed for their correlations with features of the immune microenvironment. The principal analysis algorithm was performed to calculate the DMRscores of each samples for qualification analysis.Findings: Three DNA methylation modes were revealed among 985 bladder cancer samples, and these modes are related to diverse clinical outcomes and several immune microenvironment phenotypes, e.g., immune-desert, immune-inflamed, and immune-excluded ones. Then patients were classified into high- and low-DMRscore subgroups according to the DMRscore, which was calculated based on the expression of DNA methylation related genes (DMRGs). Patients with the low-DMRscore subgroup presented a prominent survival advantage that was significantly correlated to the immune-inflamed phenotype. Further analysis revealed that patients with low DMRscores exhibited less TP53 wild mutation, lower cancer stage and molecular subtypes were mainly papillary subtypes. In addition, an independent immunotherapy cohort confirmed that DMRscore could serve as a signature to predict prognosis outcomes and immune responses.Conclusion: Global DNA methylation modes can be used to predict the immunophenotypes, aggressiveness, and immune responses of bladder cancer. DNA methylation status assessments will strengthen our insights into the features of the immune microenvironment and promote the development of more effective treatment strategies. |
| format |
article |
| author |
Fangdie Ye Fangdie Ye Yingchun Liang Yingchun Liang Jimeng Hu Jimeng Hu Yun Hu Yun Hu Yufei Liu Yufei Liu Zhang Cheng Zhang Cheng Yuxi Ou Yuxi Ou Chenyang Xu Chenyang Xu Haowen Jiang Haowen Jiang Haowen Jiang |
| author_facet |
Fangdie Ye Fangdie Ye Yingchun Liang Yingchun Liang Jimeng Hu Jimeng Hu Yun Hu Yun Hu Yufei Liu Yufei Liu Zhang Cheng Zhang Cheng Yuxi Ou Yuxi Ou Chenyang Xu Chenyang Xu Haowen Jiang Haowen Jiang Haowen Jiang |
| author_sort |
Fangdie Ye |
| title |
DNA Methylation Modification Map to Predict Tumor Molecular Subtypes and Efficacy of Immunotherapy in Bladder Cancer |
| title_short |
DNA Methylation Modification Map to Predict Tumor Molecular Subtypes and Efficacy of Immunotherapy in Bladder Cancer |
| title_full |
DNA Methylation Modification Map to Predict Tumor Molecular Subtypes and Efficacy of Immunotherapy in Bladder Cancer |
| title_fullStr |
DNA Methylation Modification Map to Predict Tumor Molecular Subtypes and Efficacy of Immunotherapy in Bladder Cancer |
| title_full_unstemmed |
DNA Methylation Modification Map to Predict Tumor Molecular Subtypes and Efficacy of Immunotherapy in Bladder Cancer |
| title_sort |
dna methylation modification map to predict tumor molecular subtypes and efficacy of immunotherapy in bladder cancer |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/227e965f12f74acab84b3886153e2f1c |
| work_keys_str_mv |
AT fangdieye dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT fangdieye dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT yingchunliang dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT yingchunliang dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT jimenghu dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT jimenghu dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT yunhu dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT yunhu dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT yufeiliu dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT yufeiliu dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT zhangcheng dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT zhangcheng dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT yuxiou dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT yuxiou dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT chenyangxu dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT chenyangxu dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT haowenjiang dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT haowenjiang dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer AT haowenjiang dnamethylationmodificationmaptopredicttumormolecularsubtypesandefficacyofimmunotherapyinbladdercancer |
| _version_ |
1718373860068294656 |