Identification of an Immune-Related Risk Signature Correlates With Immunophenotype and Predicts Anti-PD-L1 Efficacy of Urothelial Cancer
Immune checkpoint inhibitor (ICI) treatment has been used to treat advanced urothelial cancer. Molecular markers might improve risk stratification and prediction of ICI benefit for urothelial cancer patients. We analyzed 406 cases of bladder urothelial cancer from The Cancer Genome Atlas (TCGA) data...
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Frontiers Media S.A.
2021-03-01
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Series: | Frontiers in Cell and Developmental Biology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.646982/full |
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record_format |
Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pengju Li Pengju Li Shihui Hao Yongkang Ye Jinhuan Wei Yiming Tang Lei Tan Zhuangyao Liao Mingxiao Zhang Jiaying Li Chengpeng Gui Jiefei Xiao Yong Huang Xu Chen Jiazheng Cao Junhang Luo Junhang Luo Wei Chen |
spellingShingle |
Pengju Li Pengju Li Shihui Hao Yongkang Ye Jinhuan Wei Yiming Tang Lei Tan Zhuangyao Liao Mingxiao Zhang Jiaying Li Chengpeng Gui Jiefei Xiao Yong Huang Xu Chen Jiazheng Cao Junhang Luo Junhang Luo Wei Chen Identification of an Immune-Related Risk Signature Correlates With Immunophenotype and Predicts Anti-PD-L1 Efficacy of Urothelial Cancer Frontiers in Cell and Developmental Biology immune-related risk signature immunity gene immune checkpoint inhibitor urothelial cancer tumor microenvironment |
author_facet |
Pengju Li Pengju Li Shihui Hao Yongkang Ye Jinhuan Wei Yiming Tang Lei Tan Zhuangyao Liao Mingxiao Zhang Jiaying Li Chengpeng Gui Jiefei Xiao Yong Huang Xu Chen Jiazheng Cao Junhang Luo Junhang Luo Wei Chen |
author_sort |
Pengju Li |
title |
Identification of an Immune-Related Risk Signature Correlates With Immunophenotype and Predicts Anti-PD-L1 Efficacy of Urothelial Cancer |
title_short |
Identification of an Immune-Related Risk Signature Correlates With Immunophenotype and Predicts Anti-PD-L1 Efficacy of Urothelial Cancer |
title_full |
Identification of an Immune-Related Risk Signature Correlates With Immunophenotype and Predicts Anti-PD-L1 Efficacy of Urothelial Cancer |
title_fullStr |
Identification of an Immune-Related Risk Signature Correlates With Immunophenotype and Predicts Anti-PD-L1 Efficacy of Urothelial Cancer |
title_full_unstemmed |
Identification of an Immune-Related Risk Signature Correlates With Immunophenotype and Predicts Anti-PD-L1 Efficacy of Urothelial Cancer |
title_sort |
identification of an immune-related risk signature correlates with immunophenotype and predicts anti-pd-l1 efficacy of urothelial cancer |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-03-01 |
description |
Immune checkpoint inhibitor (ICI) treatment has been used to treat advanced urothelial cancer. Molecular markers might improve risk stratification and prediction of ICI benefit for urothelial cancer patients. We analyzed 406 cases of bladder urothelial cancer from The Cancer Genome Atlas (TCGA) data set and identified 161 messenger RNAs (mRNAs) as differentially expressed immunity genes (DEIGs). Using the LASSO Cox regression model, an eight-mRNA-based risk signature was built. We validated the prognostic and predictive accuracy of this immune-related risk signature in 348 metastatic urothelial cancer (mUC) samples treated with anti-PD-L1 (atezolizumab) from IMvigor210. We built an immune-related risk signature based on the eight mRNAs: ANXA1, IL22, IL9R, KLRK1, LRP1, NRG3, SEMA6D, and STAP2. The eight-mRNA-based risk signature successfully categorizes patients into high-risk and low-risk groups. Overall survival was significantly different between these groups, regardless if the initial TCGA training set, the internal TCGA testing set, all TCGA set, or the ICI treatment set. The hazard ratio (HR) of the high-risk group to the low-risk group was 3.65 (p < 0.0001), 2.56 (p < 0.0001), 3.36 (p < 0.0001), and 2.42 (p = 0.0009). The risk signature was an independent prognostic factor for prediction survival. Moreover, the risk signature was related to immunity characteristics. In different tumor mutational burden (TMB) subgroups, it successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome. Our eight-mRNA-based risk signature is a stable biomarker for urothelial cancer and might be able to predict which patients benefit from ICI treatment. It might play a role in precision individualized immunotherapy. |
topic |
immune-related risk signature immunity gene immune checkpoint inhibitor urothelial cancer tumor microenvironment |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.646982/full |
work_keys_str_mv |
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doaj-3e43884d930a42c5b1dfed867c8766dd2021-03-18T05:28:45ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-03-01910.3389/fcell.2021.646982646982Identification of an Immune-Related Risk Signature Correlates With Immunophenotype and Predicts Anti-PD-L1 Efficacy of Urothelial CancerPengju Li0Pengju Li1Shihui Hao2Yongkang Ye3Jinhuan Wei4Yiming Tang5Lei Tan6Zhuangyao Liao7Mingxiao Zhang8Jiaying Li9Chengpeng Gui10Jiefei Xiao11Yong Huang12Xu Chen13Jiazheng Cao14Junhang Luo15Junhang Luo16Wei Chen17Department of Urology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaInstitute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Urology, Dongguan People’s Hospital, Affiliated to Southern Medical University, Dongguan, ChinaDepartment of Urology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Extracorporeal Circulation, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yet-sen University, Jiangmen, ChinaDepartment of Urology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaInstitute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaImmune checkpoint inhibitor (ICI) treatment has been used to treat advanced urothelial cancer. Molecular markers might improve risk stratification and prediction of ICI benefit for urothelial cancer patients. We analyzed 406 cases of bladder urothelial cancer from The Cancer Genome Atlas (TCGA) data set and identified 161 messenger RNAs (mRNAs) as differentially expressed immunity genes (DEIGs). Using the LASSO Cox regression model, an eight-mRNA-based risk signature was built. We validated the prognostic and predictive accuracy of this immune-related risk signature in 348 metastatic urothelial cancer (mUC) samples treated with anti-PD-L1 (atezolizumab) from IMvigor210. We built an immune-related risk signature based on the eight mRNAs: ANXA1, IL22, IL9R, KLRK1, LRP1, NRG3, SEMA6D, and STAP2. The eight-mRNA-based risk signature successfully categorizes patients into high-risk and low-risk groups. Overall survival was significantly different between these groups, regardless if the initial TCGA training set, the internal TCGA testing set, all TCGA set, or the ICI treatment set. The hazard ratio (HR) of the high-risk group to the low-risk group was 3.65 (p < 0.0001), 2.56 (p < 0.0001), 3.36 (p < 0.0001), and 2.42 (p = 0.0009). The risk signature was an independent prognostic factor for prediction survival. Moreover, the risk signature was related to immunity characteristics. In different tumor mutational burden (TMB) subgroups, it successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome. Our eight-mRNA-based risk signature is a stable biomarker for urothelial cancer and might be able to predict which patients benefit from ICI treatment. It might play a role in precision individualized immunotherapy.https://www.frontiersin.org/articles/10.3389/fcell.2021.646982/fullimmune-related risk signatureimmunity geneimmune checkpoint inhibitorurothelial cancertumor microenvironment |