Construction of T cell exhaustion model for predicting survival and immunotherapy effect of bladder cancer based on WGCNA
IntroductionThe prognosis of bladder cancer (BLCA) and response to immune checkpoint inhibitors (ICIs) are determined by multiple factors. Existed biomarkers for predicting the effect of immunotherapy cannot accurately predict the response of BLCA patients to ICIs.MethodsTo further accurately strati...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1196802/full |
| _version_ | 1797815129975291904 |
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| author | Yuwen Xue Guanghui Zhao Guanghui Zhao Xiaoxin Pu Fangdong Jiao |
| author_facet | Yuwen Xue Guanghui Zhao Guanghui Zhao Xiaoxin Pu Fangdong Jiao |
| author_sort | Yuwen Xue |
| collection | DOAJ |
| description | IntroductionThe prognosis of bladder cancer (BLCA) and response to immune checkpoint inhibitors (ICIs) are determined by multiple factors. Existed biomarkers for predicting the effect of immunotherapy cannot accurately predict the response of BLCA patients to ICIs.MethodsTo further accurately stratify patients’ response to ICIs and identify potential novel predictive biomarkers, we used the known T cell exhaustion (TEX)-related specific pathways, including tumor necrosis factor (TNF), interleukin (IL)-2, interferon (IFN)-g, and T- cell cytotoxicpathways, combined with weighted correlation network analysis (WGCNA) to analyze the characteristics of TEX in BLCA in detail, constructed a TEX model.ResultsThis model including 28 genes can robustly predict the survival of BLCA and immunotherapeutic efficacy. This model could divide BLCA into two groups, TEXhigh and TEXlow, with significantly different prognoses, clinical features, and reactivity to ICIs. The critical characteristic genes, such as potential biomarkers Charged Multivesicular Body Protein 4C (CHMP4C), SH2 Domain Containing 2A (SH2D2A), Prickle Planar Cell Polarity Protein 3 (PRICKLE3) and Zinc Finger Protein 165 (ZNF165) were verified in BLCA clinical samples by real-time quantitative chain reaction (qPCR) and immunohistochemistry (IHC).DiscussionOur findings show that the TEX model can serve as biological markers for predicting the response to ICIs, and the involving molecules in the TEX model might provide new potential targets for immunotherapy in BLCA. |
| first_indexed | 2024-03-13T08:18:08Z |
| format | Article |
| id | doaj.art-dd9229ad531d471d87e0d879564af757 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-13T08:18:08Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-dd9229ad531d471d87e0d879564af7572023-05-31T13:32:28ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-05-011310.3389/fonc.2023.11968021196802Construction of T cell exhaustion model for predicting survival and immunotherapy effect of bladder cancer based on WGCNAYuwen Xue0Guanghui Zhao1Guanghui Zhao2Xiaoxin Pu3Fangdong Jiao4Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, ChinaPeking University People’s Hospital, Qingdao Women and Children’s Hospital, Qingdao, ChinaMedical Laboratory Center, Qilu Hospital (Qingdao) of Shandong University, Qingdao, ChinaDepartment of Pulmonary and Critical Care Medicine, Qilu Hospital (Qingdao) of Shandong University, Qingdao, ChinaDepartment of Urology Surgery, Qilu Hospital (Qingdao) of Shandong University, Qingdao, ChinaIntroductionThe prognosis of bladder cancer (BLCA) and response to immune checkpoint inhibitors (ICIs) are determined by multiple factors. Existed biomarkers for predicting the effect of immunotherapy cannot accurately predict the response of BLCA patients to ICIs.MethodsTo further accurately stratify patients’ response to ICIs and identify potential novel predictive biomarkers, we used the known T cell exhaustion (TEX)-related specific pathways, including tumor necrosis factor (TNF), interleukin (IL)-2, interferon (IFN)-g, and T- cell cytotoxicpathways, combined with weighted correlation network analysis (WGCNA) to analyze the characteristics of TEX in BLCA in detail, constructed a TEX model.ResultsThis model including 28 genes can robustly predict the survival of BLCA and immunotherapeutic efficacy. This model could divide BLCA into two groups, TEXhigh and TEXlow, with significantly different prognoses, clinical features, and reactivity to ICIs. The critical characteristic genes, such as potential biomarkers Charged Multivesicular Body Protein 4C (CHMP4C), SH2 Domain Containing 2A (SH2D2A), Prickle Planar Cell Polarity Protein 3 (PRICKLE3) and Zinc Finger Protein 165 (ZNF165) were verified in BLCA clinical samples by real-time quantitative chain reaction (qPCR) and immunohistochemistry (IHC).DiscussionOur findings show that the TEX model can serve as biological markers for predicting the response to ICIs, and the involving molecules in the TEX model might provide new potential targets for immunotherapy in BLCA.https://www.frontiersin.org/articles/10.3389/fonc.2023.1196802/fullbladder cancerT cell exhaustionWGCNAsurvivalimmunotherapy |
| spellingShingle | Yuwen Xue Guanghui Zhao Guanghui Zhao Xiaoxin Pu Fangdong Jiao Construction of T cell exhaustion model for predicting survival and immunotherapy effect of bladder cancer based on WGCNA Frontiers in Oncology bladder cancer T cell exhaustion WGCNA survival immunotherapy |
| title | Construction of T cell exhaustion model for predicting survival and immunotherapy effect of bladder cancer based on WGCNA |
| title_full | Construction of T cell exhaustion model for predicting survival and immunotherapy effect of bladder cancer based on WGCNA |
| title_fullStr | Construction of T cell exhaustion model for predicting survival and immunotherapy effect of bladder cancer based on WGCNA |
| title_full_unstemmed | Construction of T cell exhaustion model for predicting survival and immunotherapy effect of bladder cancer based on WGCNA |
| title_short | Construction of T cell exhaustion model for predicting survival and immunotherapy effect of bladder cancer based on WGCNA |
| title_sort | construction of t cell exhaustion model for predicting survival and immunotherapy effect of bladder cancer based on wgcna |
| topic | bladder cancer T cell exhaustion WGCNA survival immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1196802/full |
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