Cargando…

Transcriptional Profiling of Advanced Urothelial Cancer Predicts Prognosis and Response to Immunotherapy

Recent investigations reported that some subtypes from the Lund or The Cancer Genome Atlas (TCGA) classifications were most responsive to PD-L1 inhibitor treatment. However, the association between previously reported subtypes and immune checkpoint inhibitor (ICI) therapy responsiveness has been ins...

Descripción completa

Detalles Bibliográficos
Autores principales: Baek, Seung-Woo, Jang, In-Hwan, Kim, Seon-Kyu, Nam, Jong-Kil, Leem, Sun-Hee, Chu, In-Sun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084828/
https://www.ncbi.nlm.nih.gov/pubmed/32182655
http://dx.doi.org/10.3390/ijms21051850
_version_ 1783508812610666496
author Baek, Seung-Woo
Jang, In-Hwan
Kim, Seon-Kyu
Nam, Jong-Kil
Leem, Sun-Hee
Chu, In-Sun
author_facet Baek, Seung-Woo
Jang, In-Hwan
Kim, Seon-Kyu
Nam, Jong-Kil
Leem, Sun-Hee
Chu, In-Sun
author_sort Baek, Seung-Woo
collection PubMed
description Recent investigations reported that some subtypes from the Lund or The Cancer Genome Atlas (TCGA) classifications were most responsive to PD-L1 inhibitor treatment. However, the association between previously reported subtypes and immune checkpoint inhibitor (ICI) therapy responsiveness has been insufficiently explored. Despite these contributions, the ability to predict the clinical applicability of immune checkpoint inhibitor therapy in patients remains a major challenge. Here, we aimed to re-classify distinct subtypes focusing on ICI responsiveness using gene expression profiling in the IMvigor 210 cohort (n = 298). Based on the hierarchical clustering analysis, we divided advanced urothelial cancer patients into three subgroups. To confirm a prognostic impact, we performed survival analysis and estimated the prognostic value in the IMvigor 210 and TCGA cohort. The activation of CD8(+) T effector cells was common for patients of classes 2 and 3 in the TCGA and IMvigor 210 cohort. Survival analysis showed that patients of class 3 in the TCGA cohort had a poor prognosis, while patients of class 3 showed considerably prolonged survival in the IMvigor 210 cohort. One of the distinct characteristics of patients in class 3 is the inactivation of the TGFβ and YAP/TAZ pathways and activation of the cell cycle and DNA replication and DNA damage (DDR). Based on our identified transcriptional patterns and the clinical outcomes of advanced urothelial cancer patients, we constructed a schematic summary. When comparing clinical and transcriptome data, patients with downregulation of the TGFβ and YAP/TAZ pathways and upregulation of the cell cycle and DDR may be more responsive to ICI therapy.
format Online
Article
Text
id pubmed-7084828
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-70848282020-03-23 Transcriptional Profiling of Advanced Urothelial Cancer Predicts Prognosis and Response to Immunotherapy Baek, Seung-Woo Jang, In-Hwan Kim, Seon-Kyu Nam, Jong-Kil Leem, Sun-Hee Chu, In-Sun Int J Mol Sci Article Recent investigations reported that some subtypes from the Lund or The Cancer Genome Atlas (TCGA) classifications were most responsive to PD-L1 inhibitor treatment. However, the association between previously reported subtypes and immune checkpoint inhibitor (ICI) therapy responsiveness has been insufficiently explored. Despite these contributions, the ability to predict the clinical applicability of immune checkpoint inhibitor therapy in patients remains a major challenge. Here, we aimed to re-classify distinct subtypes focusing on ICI responsiveness using gene expression profiling in the IMvigor 210 cohort (n = 298). Based on the hierarchical clustering analysis, we divided advanced urothelial cancer patients into three subgroups. To confirm a prognostic impact, we performed survival analysis and estimated the prognostic value in the IMvigor 210 and TCGA cohort. The activation of CD8(+) T effector cells was common for patients of classes 2 and 3 in the TCGA and IMvigor 210 cohort. Survival analysis showed that patients of class 3 in the TCGA cohort had a poor prognosis, while patients of class 3 showed considerably prolonged survival in the IMvigor 210 cohort. One of the distinct characteristics of patients in class 3 is the inactivation of the TGFβ and YAP/TAZ pathways and activation of the cell cycle and DNA replication and DNA damage (DDR). Based on our identified transcriptional patterns and the clinical outcomes of advanced urothelial cancer patients, we constructed a schematic summary. When comparing clinical and transcriptome data, patients with downregulation of the TGFβ and YAP/TAZ pathways and upregulation of the cell cycle and DDR may be more responsive to ICI therapy. MDPI 2020-03-08 /pmc/articles/PMC7084828/ /pubmed/32182655 http://dx.doi.org/10.3390/ijms21051850 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
Baek, Seung-Woo
Jang, In-Hwan
Kim, Seon-Kyu
Nam, Jong-Kil
Leem, Sun-Hee
Chu, In-Sun
Transcriptional Profiling of Advanced Urothelial Cancer Predicts Prognosis and Response to Immunotherapy
title Transcriptional Profiling of Advanced Urothelial Cancer Predicts Prognosis and Response to Immunotherapy
title_full Transcriptional Profiling of Advanced Urothelial Cancer Predicts Prognosis and Response to Immunotherapy
title_fullStr Transcriptional Profiling of Advanced Urothelial Cancer Predicts Prognosis and Response to Immunotherapy
title_full_unstemmed Transcriptional Profiling of Advanced Urothelial Cancer Predicts Prognosis and Response to Immunotherapy
title_short Transcriptional Profiling of Advanced Urothelial Cancer Predicts Prognosis and Response to Immunotherapy
title_sort transcriptional profiling of advanced urothelial cancer predicts prognosis and response to immunotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084828/
https://www.ncbi.nlm.nih.gov/pubmed/32182655
http://dx.doi.org/10.3390/ijms21051850
work_keys_str_mv AT baekseungwoo transcriptionalprofilingofadvancedurothelialcancerpredictsprognosisandresponsetoimmunotherapy
AT janginhwan transcriptionalprofilingofadvancedurothelialcancerpredictsprognosisandresponsetoimmunotherapy
AT kimseonkyu transcriptionalprofilingofadvancedurothelialcancerpredictsprognosisandresponsetoimmunotherapy
AT namjongkil transcriptionalprofilingofadvancedurothelialcancerpredictsprognosisandresponsetoimmunotherapy
AT leemsunhee transcriptionalprofilingofadvancedurothelialcancerpredictsprognosisandresponsetoimmunotherapy
AT chuinsun transcriptionalprofilingofadvancedurothelialcancerpredictsprognosisandresponsetoimmunotherapy