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

Affiliation
Department of Oncology ,Traditional Chinese Medicine Hospital of Wuxi ,Wuxi ,China
Yuan, Kemiao;
Affiliation
Department of Neurosurgery ,Wuxi People’s Hospital Affiliated to Nanjing Medical University ,Wuxi ,China
Zhao, Songyun;
Affiliation
School of Clinical Medicine ,Yangzhou Polytechnic College ,Yangzhou ,China
Ye, Bicheng;
Affiliation
Department of Gastroenterology ,Affiliated Hospital of Jiangsu University ,Zhenjiang ,China
Wang, Qi;
Affiliation
Department of General Surgery ,Wuxi People’s Hospital Affiliated to Nanjing Medical University ,Wuxi ,China
Liu, Yuan;
Affiliation
The First Affiliated Hospital of Nanjing Medical University ,Nanjing ,China
Zhang, Pengpeng;
Affiliation
The First Affiliated Hospital of Nanjing Medical University ,Nanjing ,China
Xie, Jiaheng;
Affiliation
Southwest Medical University ,Luzhou ,China
Chi, Hao;
Affiliation
Wuxi Maternal and Child Health Care Hospital ,Wuxi ,China
Chen, Yu;
Affiliation
Department of Neurosurgery ,Wuxi People’s Hospital Affiliated to Nanjing Medical University ,Wuxi ,China
Cheng, Chao;
Affiliation
Department of Gynecology ,The First Affiliated Hospital of Nanjing Medical University ,Nanjing ,China
Liu, Jinhui

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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License Holder: Copyright © 2023 Yuan, Zhao, Ye, Wang, Liu, Zhang, Xie, Chi, Chen, Cheng and Liu.

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