Tumour microenvironment landscape and immunotherapy response in bladder cancer decoded by stromal MOXD1 based on copper-related genes signature

IntroductionWe aimed to develop a copper-related gene (CRG) signature that can be used to evaluate prognosis and guide therapeutic management in bladder cancer patients.MethodsThe raw transcriptome profiles and clinical data of 405 bladder samples were downloaded from The Cancer Genome Atlas (TCGA)...

Full description

Bibliographic Details
Main Authors: Wenhao Wang, Shan Hua, Jianying Li, Jing Zhao, Yu Zhang, Juntao Jiang, Bangmin Han
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-12-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.1081091/full
_version_ 1797979188781645824
author Wenhao Wang
Shan Hua
Jianying Li
Jing Zhao
Yu Zhang
Juntao Jiang
Bangmin Han
author_facet Wenhao Wang
Shan Hua
Jianying Li
Jing Zhao
Yu Zhang
Juntao Jiang
Bangmin Han
author_sort Wenhao Wang
collection DOAJ
description IntroductionWe aimed to develop a copper-related gene (CRG) signature that can be used to evaluate prognosis and guide therapeutic management in bladder cancer patients.MethodsThe raw transcriptome profiles and clinical data of 405 bladder samples were downloaded from The Cancer Genome Atlas (TCGA) database, and differentially expressed copper-related genes were identifified using the Molecular Signatures Database (MSigDB) database and univariate and multivariate Cox regression analysis. A multigene prognostic signature based on 14 CRGs was developed by least absolute shrinkage and selection operation (LASSO) analysis in the TCGA cohort and validated in the Gene Expression Omnibus (GEO) cohort. Multiple analyses were then conducted in which the nomograms, clinicopathological features, immune-related cell infifiltration characteristics, and therapy responses of the high- and low-risk score groups were compared.ResultsA 14 CRGs signature was constructed and used to classify patients into high-risk and low-risk groups. Compared to patients classifified as high-risk, low-risk patients in both the TCGA cohort and the GEO cohort had better overall survival. Patients in high-risk groups had more aggressive clinical features, immunologically “cold” infifiltrating characteristics, and experienced lower therapeutic effificacy. We identifified a CRG signature of bladder cancer and validated it using unsupervised clustering analysis. Monooxygenase DBH-like 1 (MOXD1) was further identifified, and its potential for evaluating the tumor immune microenvironment and predicting the immunotherapy response was explored.DiscussionThese results suggest a novel research direction for precision therapy of bladder cancer and demonstrate that copper-related genes can play a promising role in predicting prognosis and may serve as therapeutic targets for bladder cancer.
first_indexed 2024-04-11T05:35:03Z
format Article
id doaj.art-b68104bd42fa4587aae038f21a555ff2
institution Directory Open Access Journal
issn 2234-943X
language English
last_indexed 2024-04-11T05:35:03Z
publishDate 2022-12-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Oncology
spelling doaj.art-b68104bd42fa4587aae038f21a555ff22022-12-22T13:58:18ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-12-011210.3389/fonc.2022.10810911081091Tumour microenvironment landscape and immunotherapy response in bladder cancer decoded by stromal MOXD1 based on copper-related genes signatureWenhao WangShan HuaJianying LiJing ZhaoYu ZhangJuntao JiangBangmin HanIntroductionWe aimed to develop a copper-related gene (CRG) signature that can be used to evaluate prognosis and guide therapeutic management in bladder cancer patients.MethodsThe raw transcriptome profiles and clinical data of 405 bladder samples were downloaded from The Cancer Genome Atlas (TCGA) database, and differentially expressed copper-related genes were identifified using the Molecular Signatures Database (MSigDB) database and univariate and multivariate Cox regression analysis. A multigene prognostic signature based on 14 CRGs was developed by least absolute shrinkage and selection operation (LASSO) analysis in the TCGA cohort and validated in the Gene Expression Omnibus (GEO) cohort. Multiple analyses were then conducted in which the nomograms, clinicopathological features, immune-related cell infifiltration characteristics, and therapy responses of the high- and low-risk score groups were compared.ResultsA 14 CRGs signature was constructed and used to classify patients into high-risk and low-risk groups. Compared to patients classifified as high-risk, low-risk patients in both the TCGA cohort and the GEO cohort had better overall survival. Patients in high-risk groups had more aggressive clinical features, immunologically “cold” infifiltrating characteristics, and experienced lower therapeutic effificacy. We identifified a CRG signature of bladder cancer and validated it using unsupervised clustering analysis. Monooxygenase DBH-like 1 (MOXD1) was further identifified, and its potential for evaluating the tumor immune microenvironment and predicting the immunotherapy response was explored.DiscussionThese results suggest a novel research direction for precision therapy of bladder cancer and demonstrate that copper-related genes can play a promising role in predicting prognosis and may serve as therapeutic targets for bladder cancer.https://www.frontiersin.org/articles/10.3389/fonc.2022.1081091/fullbladder cancercoppersignaturetumor-infiltrating immune cellimmunotherapyfibroblast
spellingShingle Wenhao Wang
Shan Hua
Jianying Li
Jing Zhao
Yu Zhang
Juntao Jiang
Bangmin Han
Tumour microenvironment landscape and immunotherapy response in bladder cancer decoded by stromal MOXD1 based on copper-related genes signature
Frontiers in Oncology
bladder cancer
copper
signature
tumor-infiltrating immune cell
immunotherapy
fibroblast
title Tumour microenvironment landscape and immunotherapy response in bladder cancer decoded by stromal MOXD1 based on copper-related genes signature
title_full Tumour microenvironment landscape and immunotherapy response in bladder cancer decoded by stromal MOXD1 based on copper-related genes signature
title_fullStr Tumour microenvironment landscape and immunotherapy response in bladder cancer decoded by stromal MOXD1 based on copper-related genes signature
title_full_unstemmed Tumour microenvironment landscape and immunotherapy response in bladder cancer decoded by stromal MOXD1 based on copper-related genes signature
title_short Tumour microenvironment landscape and immunotherapy response in bladder cancer decoded by stromal MOXD1 based on copper-related genes signature
title_sort tumour microenvironment landscape and immunotherapy response in bladder cancer decoded by stromal moxd1 based on copper related genes signature
topic bladder cancer
copper
signature
tumor-infiltrating immune cell
immunotherapy
fibroblast
url https://www.frontiersin.org/articles/10.3389/fonc.2022.1081091/full
work_keys_str_mv AT wenhaowang tumourmicroenvironmentlandscapeandimmunotherapyresponseinbladdercancerdecodedbystromalmoxd1basedoncopperrelatedgenessignature
AT shanhua tumourmicroenvironmentlandscapeandimmunotherapyresponseinbladdercancerdecodedbystromalmoxd1basedoncopperrelatedgenessignature
AT jianyingli tumourmicroenvironmentlandscapeandimmunotherapyresponseinbladdercancerdecodedbystromalmoxd1basedoncopperrelatedgenessignature
AT jingzhao tumourmicroenvironmentlandscapeandimmunotherapyresponseinbladdercancerdecodedbystromalmoxd1basedoncopperrelatedgenessignature
AT yuzhang tumourmicroenvironmentlandscapeandimmunotherapyresponseinbladdercancerdecodedbystromalmoxd1basedoncopperrelatedgenessignature
AT juntaojiang tumourmicroenvironmentlandscapeandimmunotherapyresponseinbladdercancerdecodedbystromalmoxd1basedoncopperrelatedgenessignature
AT bangminhan tumourmicroenvironmentlandscapeandimmunotherapyresponseinbladdercancerdecodedbystromalmoxd1basedoncopperrelatedgenessignature