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Chromosomal Instability May Not Be a Predictor for Immune Checkpoint Inhibitors from a Comprehensive Bioinformatics Analysis

Immune checkpoint inhibitors (ICIs) have become the standard of care in various cancers, although their predictive tools have not yet completely developed. Here, we aimed to exam the role of 70-gene chromosomal instability signature (CIN70) in cancers, and its association with previous predictors, t...

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Autores principales: Wu, Chiao-En, Yeh, Da-Wei, Pan, Yi-Ru, Huang, Wen-Kuan, Chen, Ming-Huang, Chang, John Wen-Cheng, Chen, Jen-Shi, Wang, Yu-Chao, Yeh, Chun-Nan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695172/
https://www.ncbi.nlm.nih.gov/pubmed/33171596
http://dx.doi.org/10.3390/life10110276
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author Wu, Chiao-En
Yeh, Da-Wei
Pan, Yi-Ru
Huang, Wen-Kuan
Chen, Ming-Huang
Chang, John Wen-Cheng
Chen, Jen-Shi
Wang, Yu-Chao
Yeh, Chun-Nan
author_facet Wu, Chiao-En
Yeh, Da-Wei
Pan, Yi-Ru
Huang, Wen-Kuan
Chen, Ming-Huang
Chang, John Wen-Cheng
Chen, Jen-Shi
Wang, Yu-Chao
Yeh, Chun-Nan
author_sort Wu, Chiao-En
collection PubMed
description Immune checkpoint inhibitors (ICIs) have become the standard of care in various cancers, although their predictive tools have not yet completely developed. Here, we aimed to exam the role of 70-gene chromosomal instability signature (CIN70) in cancers, and its association with previous predictors, tumor mutation burden (TMB), and microsatellite instability (MSI), for patients undergoing ICIs, as well as the possible predictive value for ICIs. We examined the association of CIN70 with TMB and MSI, as well as the impact of these biomarkers on the survival of 33 cancer cohorts from The Cancer Genome Atlas (TCGA) databank. The predictive value of the ICIs of CIN70 in previously published reports was also validated. Using the TCGA dataset, CIN70 scores were frequently (either positively or negatively) associated with TMB, but were only significantly associated with MSI status in three types of cancer. In addition, our current study showed that all TMB, MSI, and CIN70 had their own prognostic values for survival in patients with various cancers, and that they could be cancer type-specific. In two validation cohorts (melanoma by Hugo et al. and urothelial cancer by Snyder et al.), no significant difference of CIN70 scores was found between responders and non-responders (p-value = 0.226 and 0.108, respectively). In addition, no overall survival difference was noted between patients with a high CIN70 and those with a low CIN70 (p-value = 0.106 and 0.222, respectively). In conclusion, the current study, through a comprehensive bioinformatics analysis, demonstrated a correlation between CIN70 and TMB, but CIN70 is not the predictor for cancer patients undergoing ICIs. Future prospective studies are warranted to validate these findings.
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spelling pubmed-76951722020-11-28 Chromosomal Instability May Not Be a Predictor for Immune Checkpoint Inhibitors from a Comprehensive Bioinformatics Analysis Wu, Chiao-En Yeh, Da-Wei Pan, Yi-Ru Huang, Wen-Kuan Chen, Ming-Huang Chang, John Wen-Cheng Chen, Jen-Shi Wang, Yu-Chao Yeh, Chun-Nan Life (Basel) Article Immune checkpoint inhibitors (ICIs) have become the standard of care in various cancers, although their predictive tools have not yet completely developed. Here, we aimed to exam the role of 70-gene chromosomal instability signature (CIN70) in cancers, and its association with previous predictors, tumor mutation burden (TMB), and microsatellite instability (MSI), for patients undergoing ICIs, as well as the possible predictive value for ICIs. We examined the association of CIN70 with TMB and MSI, as well as the impact of these biomarkers on the survival of 33 cancer cohorts from The Cancer Genome Atlas (TCGA) databank. The predictive value of the ICIs of CIN70 in previously published reports was also validated. Using the TCGA dataset, CIN70 scores were frequently (either positively or negatively) associated with TMB, but were only significantly associated with MSI status in three types of cancer. In addition, our current study showed that all TMB, MSI, and CIN70 had their own prognostic values for survival in patients with various cancers, and that they could be cancer type-specific. In two validation cohorts (melanoma by Hugo et al. and urothelial cancer by Snyder et al.), no significant difference of CIN70 scores was found between responders and non-responders (p-value = 0.226 and 0.108, respectively). In addition, no overall survival difference was noted between patients with a high CIN70 and those with a low CIN70 (p-value = 0.106 and 0.222, respectively). In conclusion, the current study, through a comprehensive bioinformatics analysis, demonstrated a correlation between CIN70 and TMB, but CIN70 is not the predictor for cancer patients undergoing ICIs. Future prospective studies are warranted to validate these findings. MDPI 2020-11-08 /pmc/articles/PMC7695172/ /pubmed/33171596 http://dx.doi.org/10.3390/life10110276 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wu, Chiao-En
Yeh, Da-Wei
Pan, Yi-Ru
Huang, Wen-Kuan
Chen, Ming-Huang
Chang, John Wen-Cheng
Chen, Jen-Shi
Wang, Yu-Chao
Yeh, Chun-Nan
Chromosomal Instability May Not Be a Predictor for Immune Checkpoint Inhibitors from a Comprehensive Bioinformatics Analysis
title Chromosomal Instability May Not Be a Predictor for Immune Checkpoint Inhibitors from a Comprehensive Bioinformatics Analysis
title_full Chromosomal Instability May Not Be a Predictor for Immune Checkpoint Inhibitors from a Comprehensive Bioinformatics Analysis
title_fullStr Chromosomal Instability May Not Be a Predictor for Immune Checkpoint Inhibitors from a Comprehensive Bioinformatics Analysis
title_full_unstemmed Chromosomal Instability May Not Be a Predictor for Immune Checkpoint Inhibitors from a Comprehensive Bioinformatics Analysis
title_short Chromosomal Instability May Not Be a Predictor for Immune Checkpoint Inhibitors from a Comprehensive Bioinformatics Analysis
title_sort chromosomal instability may not be a predictor for immune checkpoint inhibitors from a comprehensive bioinformatics analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695172/
https://www.ncbi.nlm.nih.gov/pubmed/33171596
http://dx.doi.org/10.3390/life10110276
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