Cargando…
Biological Pathway-Derived TMB Robustly Predicts the Outcome of Immune Checkpoint Blockade Therapy
Although immune checkpoint blockade (ICB) therapies have achieved great progress, the patient response varies among cancers. In this study, we analyzed the potential genomic indicators contributing to ICB therapy response. The results showed that high tumor mutation burden (TMB) failed to predict re...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496944/ https://www.ncbi.nlm.nih.gov/pubmed/36139377 http://dx.doi.org/10.3390/cells11182802 |
_version_ | 1784794395509260288 |
---|---|
author | Miao, Ya-Ru Liu, Chun-Jie Hu, Hui Yang, Mei Guo, An-Yuan |
author_facet | Miao, Ya-Ru Liu, Chun-Jie Hu, Hui Yang, Mei Guo, An-Yuan |
author_sort | Miao, Ya-Ru |
collection | PubMed |
description | Although immune checkpoint blockade (ICB) therapies have achieved great progress, the patient response varies among cancers. In this study, we analyzed the potential genomic indicators contributing to ICB therapy response. The results showed that high tumor mutation burden (TMB) failed to predict response in anti-PD1 treated melanoma. SERPINB3 was the most significant response-related gene in melanoma and mutations in either SERPINB3 or PEG3 can serve as an independent risk factor in melanoma. Some recurrent mutations in CSMD3 were only in responders or non-responders, indicating their diverse impacts on patient response. Enrichment scores (ES) of gene mutations in 12 biological pathways were significantly higher in responders or non-responders. Next, the P-TMB calculated from genes in these pathways was significantly related to patient response with prediction AUC 0.74–0.82 in all collected datasets. In conclusion, our work provides new insights into the application of TMB in predicting patient response, which will benefit to immunotherapy research. |
format | Online Article Text |
id | pubmed-9496944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94969442022-09-23 Biological Pathway-Derived TMB Robustly Predicts the Outcome of Immune Checkpoint Blockade Therapy Miao, Ya-Ru Liu, Chun-Jie Hu, Hui Yang, Mei Guo, An-Yuan Cells Article Although immune checkpoint blockade (ICB) therapies have achieved great progress, the patient response varies among cancers. In this study, we analyzed the potential genomic indicators contributing to ICB therapy response. The results showed that high tumor mutation burden (TMB) failed to predict response in anti-PD1 treated melanoma. SERPINB3 was the most significant response-related gene in melanoma and mutations in either SERPINB3 or PEG3 can serve as an independent risk factor in melanoma. Some recurrent mutations in CSMD3 were only in responders or non-responders, indicating their diverse impacts on patient response. Enrichment scores (ES) of gene mutations in 12 biological pathways were significantly higher in responders or non-responders. Next, the P-TMB calculated from genes in these pathways was significantly related to patient response with prediction AUC 0.74–0.82 in all collected datasets. In conclusion, our work provides new insights into the application of TMB in predicting patient response, which will benefit to immunotherapy research. MDPI 2022-09-08 /pmc/articles/PMC9496944/ /pubmed/36139377 http://dx.doi.org/10.3390/cells11182802 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Miao, Ya-Ru Liu, Chun-Jie Hu, Hui Yang, Mei Guo, An-Yuan Biological Pathway-Derived TMB Robustly Predicts the Outcome of Immune Checkpoint Blockade Therapy |
title | Biological Pathway-Derived TMB Robustly Predicts the Outcome of Immune Checkpoint Blockade Therapy |
title_full | Biological Pathway-Derived TMB Robustly Predicts the Outcome of Immune Checkpoint Blockade Therapy |
title_fullStr | Biological Pathway-Derived TMB Robustly Predicts the Outcome of Immune Checkpoint Blockade Therapy |
title_full_unstemmed | Biological Pathway-Derived TMB Robustly Predicts the Outcome of Immune Checkpoint Blockade Therapy |
title_short | Biological Pathway-Derived TMB Robustly Predicts the Outcome of Immune Checkpoint Blockade Therapy |
title_sort | biological pathway-derived tmb robustly predicts the outcome of immune checkpoint blockade therapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496944/ https://www.ncbi.nlm.nih.gov/pubmed/36139377 http://dx.doi.org/10.3390/cells11182802 |
work_keys_str_mv | AT miaoyaru biologicalpathwayderivedtmbrobustlypredictstheoutcomeofimmunecheckpointblockadetherapy AT liuchunjie biologicalpathwayderivedtmbrobustlypredictstheoutcomeofimmunecheckpointblockadetherapy AT huhui biologicalpathwayderivedtmbrobustlypredictstheoutcomeofimmunecheckpointblockadetherapy AT yangmei biologicalpathwayderivedtmbrobustlypredictstheoutcomeofimmunecheckpointblockadetherapy AT guoanyuan biologicalpathwayderivedtmbrobustlypredictstheoutcomeofimmunecheckpointblockadetherapy |