Identification and validation of T cell senescence-related prognostic genes in gastric carcinoma and investigation of their potential regulatory mechanisms

Abstract Objective This study aimed to identify prognostic genes associated with immunosenescence in gastric carcinoma (GC) and to elucidate their mechanisms to provide new ideas for the clinical treatment of GC. Methods According to single cell data, clustering and annotation were conducted to acqu...

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Main Authors: Jing Liu, Huiyu Wang, Fang Huang, Zhiqiang Hang, Pan Xu, Runjie Wang, Junying Xu
Format: Article
Language:English
Published: Springer 2025-06-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02477-4
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author Jing Liu
Huiyu Wang
Fang Huang
Zhiqiang Hang
Pan Xu
Runjie Wang
Junying Xu
author_facet Jing Liu
Huiyu Wang
Fang Huang
Zhiqiang Hang
Pan Xu
Runjie Wang
Junying Xu
author_sort Jing Liu
collection DOAJ
description Abstract Objective This study aimed to identify prognostic genes associated with immunosenescence in gastric carcinoma (GC) and to elucidate their mechanisms to provide new ideas for the clinical treatment of GC. Methods According to single cell data, clustering and annotation were conducted to acquire key cells. Then, differentially expressed genes (DEGs) in key cells (KC-DEGs) and TCGA-GC (GC-DEGs) were obtained, and took their intersection with CS-RGs to obtain candidate genes. Afterwards, prognostic genes were identified by regression analyses. Following this, the risk model was constructed, and the high-risk and low-risk groups were obtained. Next, a nomogram based on independent prognostic factors was constructed for predicting survival in GC. Finally, to further explore the mechanisms associated with the risk groups, immune microenvironment analysis was performed. Results T cells were used as key cells. Subsequently, AXL, PIM1, STK40, CXCL1, IFNG and SERPINE1 were identified as prognostic genes. The risk model and nomogram had favourable predictive capability in survival of GC patients. Surprisingly, 17 differential immune cells had higher levels of infiltration in the high-risk group, a result that was further confirmed in tumor purity. Notably, there was mostly a positive correlation between them and prognostic genes. Then, both tumor mutation burden (TMB) and microsatellite instability (MSI) were lower in the high-risk group, suggested the high-risk group might be associated with lower treatment benefit. Conclusion 6 prognostic genes were identified, providing novel concepts in prognosis and therapy for GC.
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spelling doaj-art-5abc40a0c40942ecaf5965ccd7d44ba12025-08-20T02:05:13ZengSpringerDiscover Oncology2730-60112025-06-0116111710.1007/s12672-025-02477-4Identification and validation of T cell senescence-related prognostic genes in gastric carcinoma and investigation of their potential regulatory mechanismsJing Liu0Huiyu Wang1Fang Huang2Zhiqiang Hang3Pan Xu4Runjie Wang5Junying Xu6 Department of Oncology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University Department of Oncology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University Department of Oncology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University Department of Oncology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University Department of Oncology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University Department of Oncology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University Department of Oncology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical UniversityAbstract Objective This study aimed to identify prognostic genes associated with immunosenescence in gastric carcinoma (GC) and to elucidate their mechanisms to provide new ideas for the clinical treatment of GC. Methods According to single cell data, clustering and annotation were conducted to acquire key cells. Then, differentially expressed genes (DEGs) in key cells (KC-DEGs) and TCGA-GC (GC-DEGs) were obtained, and took their intersection with CS-RGs to obtain candidate genes. Afterwards, prognostic genes were identified by regression analyses. Following this, the risk model was constructed, and the high-risk and low-risk groups were obtained. Next, a nomogram based on independent prognostic factors was constructed for predicting survival in GC. Finally, to further explore the mechanisms associated with the risk groups, immune microenvironment analysis was performed. Results T cells were used as key cells. Subsequently, AXL, PIM1, STK40, CXCL1, IFNG and SERPINE1 were identified as prognostic genes. The risk model and nomogram had favourable predictive capability in survival of GC patients. Surprisingly, 17 differential immune cells had higher levels of infiltration in the high-risk group, a result that was further confirmed in tumor purity. Notably, there was mostly a positive correlation between them and prognostic genes. Then, both tumor mutation burden (TMB) and microsatellite instability (MSI) were lower in the high-risk group, suggested the high-risk group might be associated with lower treatment benefit. Conclusion 6 prognostic genes were identified, providing novel concepts in prognosis and therapy for GC.https://doi.org/10.1007/s12672-025-02477-4Gastric carcinomaImmunosenescencePrognostic genesRisk modelSingle cell RNA sequencing data analysis
spellingShingle Jing Liu
Huiyu Wang
Fang Huang
Zhiqiang Hang
Pan Xu
Runjie Wang
Junying Xu
Identification and validation of T cell senescence-related prognostic genes in gastric carcinoma and investigation of their potential regulatory mechanisms
Discover Oncology
Gastric carcinoma
Immunosenescence
Prognostic genes
Risk model
Single cell RNA sequencing data analysis
title Identification and validation of T cell senescence-related prognostic genes in gastric carcinoma and investigation of their potential regulatory mechanisms
title_full Identification and validation of T cell senescence-related prognostic genes in gastric carcinoma and investigation of their potential regulatory mechanisms
title_fullStr Identification and validation of T cell senescence-related prognostic genes in gastric carcinoma and investigation of their potential regulatory mechanisms
title_full_unstemmed Identification and validation of T cell senescence-related prognostic genes in gastric carcinoma and investigation of their potential regulatory mechanisms
title_short Identification and validation of T cell senescence-related prognostic genes in gastric carcinoma and investigation of their potential regulatory mechanisms
title_sort identification and validation of t cell senescence related prognostic genes in gastric carcinoma and investigation of their potential regulatory mechanisms
topic Gastric carcinoma
Immunosenescence
Prognostic genes
Risk model
Single cell RNA sequencing data analysis
url https://doi.org/10.1007/s12672-025-02477-4
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