Transcriptional profiling of advanced urothelial cancer predicts prognosis and response to immunotherapy

Cited 5 time in scopus
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Title
Transcriptional profiling of advanced urothelial cancer predicts prognosis and response to immunotherapy
Author(s)
Seung Woo Baek; In Hwan Jang; Seon-Kyu Kim; J K Nam; S H Leem; In-Sun Chu
Bibliographic Citation
International Journal of Molecular Sciences, vol. 21, no. 5, pp. 1850-1850
Publication Year
2020
Abstract
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.
Keyword
CD8+ T effector cellsbladder cancerimmune checkpoint inhibitor
ISSN
1422-0067
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/ijms21051850
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
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