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A single-sample mRNA molecular classification of bladder cancer predicting prognosis and response to immunotherapy

BACKGROUND: As an immunogenic cancer, crosstalk between cancer cells and immune cells has been gradually recognized in bladder cancer (BC). Several studies have emphasized the clinical significance of the molecular stratification of BC without highlighting the role of the immune microenvironment. Al...

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Autores principales: Jin, Kun, He, Mingjing, Chen, Bo, Zhou, Xianghong, Zhang, Chichen, Zhang, Zilong, Hu, Dan, Jiang, Zhongyuan, Wei, Qiang, Qiu, Shi, Yang, Lu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360513/
https://www.ncbi.nlm.nih.gov/pubmed/35958899
http://dx.doi.org/10.21037/tau-21-887
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author Jin, Kun
He, Mingjing
Chen, Bo
Zhou, Xianghong
Zhang, Chichen
Zhang, Zilong
Hu, Dan
Jiang, Zhongyuan
Wei, Qiang
Qiu, Shi
Yang, Lu
author_facet Jin, Kun
He, Mingjing
Chen, Bo
Zhou, Xianghong
Zhang, Chichen
Zhang, Zilong
Hu, Dan
Jiang, Zhongyuan
Wei, Qiang
Qiu, Shi
Yang, Lu
author_sort Jin, Kun
collection PubMed
description BACKGROUND: As an immunogenic cancer, crosstalk between cancer cells and immune cells has been gradually recognized in bladder cancer (BC). Several studies have emphasized the clinical significance of the molecular stratification of BC without highlighting the role of the immune microenvironment. Although immunotherapy acted as a prospective treatment, more precise molecular stratification should be established to select those sensitive to immunotherapy. METHODS: To select specific immune genes forming subtypes indicating disparate prognoses, we performed bioinformatic analysis using BC transcriptomic profiles from six published datasets, with 408 BC samples in The Cancer Genome Atlas (TCGA) database and 295 individuals in International Cancer Genome Consortium (ICGC) database. Survival analyses were conducted using Kaplan-Meier curves, while Kruskal-Wallis tests were applied to test the differences among groups. Except for unsupervised clustering based on the differential expression of genes, we additionally performed binomial logistic regression, focusing on the mRNA level of a single sample. RESULTS: Unsupervised clustering showed that 4 clusters captured the best segmentation. After validation with survival data and simplification using binomial logistic regression, we found that cluster B and cluster D showed worse survival outcomes (P=0.012). Considering the similar survival outcomes of these two clusters, we recombined and performed another survival analysis, which also showed significant survival differences (P=0.0041). Bonding with clinical data, a greater proportion of risk factors were assigned to the worse prognosis subtype, especially showing higher grades in the subtype (P<0.001). In addition, immune cell infiltration, single nucleotide polymorphism (SNP) and copy number variation (CNV) all showed differences between clusters, indicating changes in the immune microenvironment and mutation burden. Through phenotypical analysis, we found metabolism and proliferation phenotypes associated with the immune clusters and mutually exclusive in BC, of which proliferation contributed to worse outcomes. Using the tumor immune dysfunction and exclusion (TIDE) score, a worse immunotherapy benefit was predicted in clusters B&D, defined as the worse prognosis subtype. CONCLUSIONS: With this novel clustering criterion based on immune-related genes, we provide a better understanding of the immune microenvironment, further guiding the use of immunotherapy.
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spelling pubmed-93605132022-08-10 A single-sample mRNA molecular classification of bladder cancer predicting prognosis and response to immunotherapy Jin, Kun He, Mingjing Chen, Bo Zhou, Xianghong Zhang, Chichen Zhang, Zilong Hu, Dan Jiang, Zhongyuan Wei, Qiang Qiu, Shi Yang, Lu Transl Androl Urol Original Article BACKGROUND: As an immunogenic cancer, crosstalk between cancer cells and immune cells has been gradually recognized in bladder cancer (BC). Several studies have emphasized the clinical significance of the molecular stratification of BC without highlighting the role of the immune microenvironment. Although immunotherapy acted as a prospective treatment, more precise molecular stratification should be established to select those sensitive to immunotherapy. METHODS: To select specific immune genes forming subtypes indicating disparate prognoses, we performed bioinformatic analysis using BC transcriptomic profiles from six published datasets, with 408 BC samples in The Cancer Genome Atlas (TCGA) database and 295 individuals in International Cancer Genome Consortium (ICGC) database. Survival analyses were conducted using Kaplan-Meier curves, while Kruskal-Wallis tests were applied to test the differences among groups. Except for unsupervised clustering based on the differential expression of genes, we additionally performed binomial logistic regression, focusing on the mRNA level of a single sample. RESULTS: Unsupervised clustering showed that 4 clusters captured the best segmentation. After validation with survival data and simplification using binomial logistic regression, we found that cluster B and cluster D showed worse survival outcomes (P=0.012). Considering the similar survival outcomes of these two clusters, we recombined and performed another survival analysis, which also showed significant survival differences (P=0.0041). Bonding with clinical data, a greater proportion of risk factors were assigned to the worse prognosis subtype, especially showing higher grades in the subtype (P<0.001). In addition, immune cell infiltration, single nucleotide polymorphism (SNP) and copy number variation (CNV) all showed differences between clusters, indicating changes in the immune microenvironment and mutation burden. Through phenotypical analysis, we found metabolism and proliferation phenotypes associated with the immune clusters and mutually exclusive in BC, of which proliferation contributed to worse outcomes. Using the tumor immune dysfunction and exclusion (TIDE) score, a worse immunotherapy benefit was predicted in clusters B&D, defined as the worse prognosis subtype. CONCLUSIONS: With this novel clustering criterion based on immune-related genes, we provide a better understanding of the immune microenvironment, further guiding the use of immunotherapy. AME Publishing Company 2022-07 /pmc/articles/PMC9360513/ /pubmed/35958899 http://dx.doi.org/10.21037/tau-21-887 Text en 2022 Translational Andrology and Urology. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Jin, Kun
He, Mingjing
Chen, Bo
Zhou, Xianghong
Zhang, Chichen
Zhang, Zilong
Hu, Dan
Jiang, Zhongyuan
Wei, Qiang
Qiu, Shi
Yang, Lu
A single-sample mRNA molecular classification of bladder cancer predicting prognosis and response to immunotherapy
title A single-sample mRNA molecular classification of bladder cancer predicting prognosis and response to immunotherapy
title_full A single-sample mRNA molecular classification of bladder cancer predicting prognosis and response to immunotherapy
title_fullStr A single-sample mRNA molecular classification of bladder cancer predicting prognosis and response to immunotherapy
title_full_unstemmed A single-sample mRNA molecular classification of bladder cancer predicting prognosis and response to immunotherapy
title_short A single-sample mRNA molecular classification of bladder cancer predicting prognosis and response to immunotherapy
title_sort single-sample mrna molecular classification of bladder cancer predicting prognosis and response to immunotherapy
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360513/
https://www.ncbi.nlm.nih.gov/pubmed/35958899
http://dx.doi.org/10.21037/tau-21-887
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