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Classification of Muscle-Invasive Bladder Cancer Based on Immunogenomic Profiling
There is a significant heterogeneity in the immunotherapeutic responsiveness of each muscle-invasive bladder cancer (MIBC) patient. In our research, we aimed to identify a novel classification of MIBC based on immunogenomic profiling that may facilitate the reasonable stratification of prognosis and...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461944/ https://www.ncbi.nlm.nih.gov/pubmed/32974156 http://dx.doi.org/10.3389/fonc.2020.01429 |
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author | Zhou, Xianghong Qiu, Shi Nie, Ling Jin, Di Jin, Kun Zheng, Xiaonan Yang, Lu Wei, Qiang |
author_facet | Zhou, Xianghong Qiu, Shi Nie, Ling Jin, Di Jin, Kun Zheng, Xiaonan Yang, Lu Wei, Qiang |
author_sort | Zhou, Xianghong |
collection | PubMed |
description | There is a significant heterogeneity in the immunotherapeutic responsiveness of each muscle-invasive bladder cancer (MIBC) patient. In our research, we aimed to identify a novel classification of MIBC based on immunogenomic profiling that may facilitate the reasonable stratification of prognosis and response to immunotherapy. The single-sample gene-set enrichment analysis (ssGSEA) was used to analyze the RNA-seq data of 29 important immune signatures from TCGA. Unsupervised hierarchical clustering was performed to identify an immunogenomic classification of MIBC. Then, we assessed the features of the classification in prognosis, immune infiltration, tumor-infiltration lymphocytes, HLA genes, and PD-L1 expression level. A total of 399 MIBC samples were included and three subtypes named Immunity_High, Immunity_Medium, and Immunity_Low were identified. The Immunity_High had a significant advantage in overall survival over the Immunity_Medium and Immunity_Low (p = 0.046 and p = 0.024). From Immunity_Low to Immunity_High, immune cell infiltration and stromal content showed an upward trend (p < 0.001). Meanwhile, Immunity_High was associated with a significantly higher proportion of TILs including dendritic cells resting, macrophages M1, mast cells resting, T cells CD4 memory activated, and T cells CD8(+). And the expression levels of all HLA genes and PD-L1 of Immunity_High were the highest, consistent (p < 0.001). Two hundred ninety eight MIBC patients treated with immunotherapy from the IMvigor210 were included to form an independent validation cohort to verify the robustness of immunogenomic classification and the ability to predict the response to immunotherapy. This classification had potential clinical implications for predicting prognosis and immunotherapeutic responsiveness of MIBC patients. |
format | Online Article Text |
id | pubmed-7461944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74619442020-09-23 Classification of Muscle-Invasive Bladder Cancer Based on Immunogenomic Profiling Zhou, Xianghong Qiu, Shi Nie, Ling Jin, Di Jin, Kun Zheng, Xiaonan Yang, Lu Wei, Qiang Front Oncol Oncology There is a significant heterogeneity in the immunotherapeutic responsiveness of each muscle-invasive bladder cancer (MIBC) patient. In our research, we aimed to identify a novel classification of MIBC based on immunogenomic profiling that may facilitate the reasonable stratification of prognosis and response to immunotherapy. The single-sample gene-set enrichment analysis (ssGSEA) was used to analyze the RNA-seq data of 29 important immune signatures from TCGA. Unsupervised hierarchical clustering was performed to identify an immunogenomic classification of MIBC. Then, we assessed the features of the classification in prognosis, immune infiltration, tumor-infiltration lymphocytes, HLA genes, and PD-L1 expression level. A total of 399 MIBC samples were included and three subtypes named Immunity_High, Immunity_Medium, and Immunity_Low were identified. The Immunity_High had a significant advantage in overall survival over the Immunity_Medium and Immunity_Low (p = 0.046 and p = 0.024). From Immunity_Low to Immunity_High, immune cell infiltration and stromal content showed an upward trend (p < 0.001). Meanwhile, Immunity_High was associated with a significantly higher proportion of TILs including dendritic cells resting, macrophages M1, mast cells resting, T cells CD4 memory activated, and T cells CD8(+). And the expression levels of all HLA genes and PD-L1 of Immunity_High were the highest, consistent (p < 0.001). Two hundred ninety eight MIBC patients treated with immunotherapy from the IMvigor210 were included to form an independent validation cohort to verify the robustness of immunogenomic classification and the ability to predict the response to immunotherapy. This classification had potential clinical implications for predicting prognosis and immunotherapeutic responsiveness of MIBC patients. Frontiers Media S.A. 2020-08-18 /pmc/articles/PMC7461944/ /pubmed/32974156 http://dx.doi.org/10.3389/fonc.2020.01429 Text en Copyright © 2020 Zhou, Qiu, Nie, Jin, Jin, Zheng, Yang and Wei. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Zhou, Xianghong Qiu, Shi Nie, Ling Jin, Di Jin, Kun Zheng, Xiaonan Yang, Lu Wei, Qiang Classification of Muscle-Invasive Bladder Cancer Based on Immunogenomic Profiling |
title | Classification of Muscle-Invasive Bladder Cancer Based on Immunogenomic Profiling |
title_full | Classification of Muscle-Invasive Bladder Cancer Based on Immunogenomic Profiling |
title_fullStr | Classification of Muscle-Invasive Bladder Cancer Based on Immunogenomic Profiling |
title_full_unstemmed | Classification of Muscle-Invasive Bladder Cancer Based on Immunogenomic Profiling |
title_short | Classification of Muscle-Invasive Bladder Cancer Based on Immunogenomic Profiling |
title_sort | classification of muscle-invasive bladder cancer based on immunogenomic profiling |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461944/ https://www.ncbi.nlm.nih.gov/pubmed/32974156 http://dx.doi.org/10.3389/fonc.2020.01429 |
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