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A novel T-cell exhaustion-related feature can accurately predict the prognosis of OC patients

The phenomenon of T Cell exhaustion (TEX) entails a progressive deterioration in the functionality of T cells within the immune system during prolonged conflicts with chronic infections or tumors. In the context of ovarian cancer immunotherapy, the development, and outcome of treatment are closely l...

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Autores principales: Yuan, Kemiao, Zhao, Songyun, Ye, Bicheng, Wang, Qi, Liu, Yuan, Zhang, Pengpeng, Xie, Jiaheng, Chi, Hao, Chen, Yu, Cheng, Chao, Liu, Jinhui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10239809/
https://www.ncbi.nlm.nih.gov/pubmed/37284314
http://dx.doi.org/10.3389/fphar.2023.1192777
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author Yuan, Kemiao
Zhao, Songyun
Ye, Bicheng
Wang, Qi
Liu, Yuan
Zhang, Pengpeng
Xie, Jiaheng
Chi, Hao
Chen, Yu
Cheng, Chao
Liu, Jinhui
author_facet Yuan, Kemiao
Zhao, Songyun
Ye, Bicheng
Wang, Qi
Liu, Yuan
Zhang, Pengpeng
Xie, Jiaheng
Chi, Hao
Chen, Yu
Cheng, Chao
Liu, Jinhui
author_sort Yuan, Kemiao
collection PubMed
description The phenomenon of T Cell exhaustion (TEX) entails a progressive deterioration in the functionality of T cells within the immune system during prolonged conflicts with chronic infections or tumors. In the context of ovarian cancer immunotherapy, the development, and outcome of treatment are closely linked to T-cell exhaustion. Hence, gaining an in-depth understanding of the features of TEX within the immune microenvironment of ovarian cancer is of paramount importance for the management of OC patients. To this end, we leveraged single-cell RNA data from OC to perform clustering and identify T-cell marker genes utilizing the Unified Modal Approximation and Projection (UMAP) approach. Through GSVA and WGCNA in bulk RNA-seq data, we identified 185 TEX-related genes (TEXRGs). Subsequently, we transformed ten machine learning algorithms into 80 combinations and selected the most optimal one to construct TEX-related prognostic features (TEXRPS) based on the mean C-index of the three OC cohorts. In addition, we explored the disparities in clinicopathological features, mutational status, immune cell infiltration, and immunotherapy efficacy between the high-risk (HR) and low-risk (LR) groups. Upon the integration of clinicopathological features, TEXRPS displayed robust predictive power. Notably, patients in the LR group exhibited a superior prognosis, higher tumor mutational load (TMB), greater immune cell infiltration abundance, and enhanced sensitivity to immunotherapy. Lastly, we verified the differential expression of the model gene CD44 using qRT-PCR. In conclusion, our study offers a valuable tool to guide clinical management and targeted therapy of OC.
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spelling pubmed-102398092023-06-06 A novel T-cell exhaustion-related feature can accurately predict the prognosis of OC patients Yuan, Kemiao Zhao, Songyun Ye, Bicheng Wang, Qi Liu, Yuan Zhang, Pengpeng Xie, Jiaheng Chi, Hao Chen, Yu Cheng, Chao Liu, Jinhui Front Pharmacol Pharmacology The phenomenon of T Cell exhaustion (TEX) entails a progressive deterioration in the functionality of T cells within the immune system during prolonged conflicts with chronic infections or tumors. In the context of ovarian cancer immunotherapy, the development, and outcome of treatment are closely linked to T-cell exhaustion. Hence, gaining an in-depth understanding of the features of TEX within the immune microenvironment of ovarian cancer is of paramount importance for the management of OC patients. To this end, we leveraged single-cell RNA data from OC to perform clustering and identify T-cell marker genes utilizing the Unified Modal Approximation and Projection (UMAP) approach. Through GSVA and WGCNA in bulk RNA-seq data, we identified 185 TEX-related genes (TEXRGs). Subsequently, we transformed ten machine learning algorithms into 80 combinations and selected the most optimal one to construct TEX-related prognostic features (TEXRPS) based on the mean C-index of the three OC cohorts. In addition, we explored the disparities in clinicopathological features, mutational status, immune cell infiltration, and immunotherapy efficacy between the high-risk (HR) and low-risk (LR) groups. Upon the integration of clinicopathological features, TEXRPS displayed robust predictive power. Notably, patients in the LR group exhibited a superior prognosis, higher tumor mutational load (TMB), greater immune cell infiltration abundance, and enhanced sensitivity to immunotherapy. Lastly, we verified the differential expression of the model gene CD44 using qRT-PCR. In conclusion, our study offers a valuable tool to guide clinical management and targeted therapy of OC. Frontiers Media S.A. 2023-05-22 /pmc/articles/PMC10239809/ /pubmed/37284314 http://dx.doi.org/10.3389/fphar.2023.1192777 Text en Copyright © 2023 Yuan, Zhao, Ye, Wang, Liu, Zhang, Xie, Chi, Chen, Cheng and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Yuan, Kemiao
Zhao, Songyun
Ye, Bicheng
Wang, Qi
Liu, Yuan
Zhang, Pengpeng
Xie, Jiaheng
Chi, Hao
Chen, Yu
Cheng, Chao
Liu, Jinhui
A novel T-cell exhaustion-related feature can accurately predict the prognosis of OC patients
title A novel T-cell exhaustion-related feature can accurately predict the prognosis of OC patients
title_full A novel T-cell exhaustion-related feature can accurately predict the prognosis of OC patients
title_fullStr A novel T-cell exhaustion-related feature can accurately predict the prognosis of OC patients
title_full_unstemmed A novel T-cell exhaustion-related feature can accurately predict the prognosis of OC patients
title_short A novel T-cell exhaustion-related feature can accurately predict the prognosis of OC patients
title_sort novel t-cell exhaustion-related feature can accurately predict the prognosis of oc patients
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10239809/
https://www.ncbi.nlm.nih.gov/pubmed/37284314
http://dx.doi.org/10.3389/fphar.2023.1192777
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