Chaperonin containing TCP1 subunit 5 as a novel pan-cancer prognostic biomarker for tumor stemness and immunotherapy response: insights from multi-omics data, integrated machine learning, and experimental validation
Abstract Background Chaperonin containing TCP1 subunit 5 (CCT5), a vital component of the molecular chaperonin complex, has been implicated in tumorigenesis, cancer stemness maintenance, and therapeutic resistance. Nevertheless, its comprehensive roles in pan-cancer progression, underlying biologica...
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| Format: | Article |
| Language: | English |
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Springer
2025-05-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-025-04071-7 |
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| author | Jiajun Li Nuo Xu Leyin Hu Jiayue Xu Yifan Huang Deqi Wang Feng Chen Yi Wang Jiani Jiang Yanggang Hong Huajun Ye |
| author_facet | Jiajun Li Nuo Xu Leyin Hu Jiayue Xu Yifan Huang Deqi Wang Feng Chen Yi Wang Jiani Jiang Yanggang Hong Huajun Ye |
| author_sort | Jiajun Li |
| collection | DOAJ |
| description | Abstract Background Chaperonin containing TCP1 subunit 5 (CCT5), a vital component of the molecular chaperonin complex, has been implicated in tumorigenesis, cancer stemness maintenance, and therapeutic resistance. Nevertheless, its comprehensive roles in pan-cancer progression, underlying biological functions, and potential as a predictor of immunotherapy response remains poorly understood. Methods We performed a comprehensive multi-omics pan-cancer analysis of CCT5 across 33 cancer types, integrating bulk RNA-seq, single-cell RNA-seq (scRNA-seq), and spatial transcriptomics data. CCT5 expression patterns, prognostic relevance, stemness association, and immune microenvironment relationships were evaluated. A novel CCT5-based signature (CCT5.Sig) was developed using machine learning on 23 immune checkpoint blockade (ICB) cohorts (n = 1394) spanning eight cancer types. Model performance was assessed using AUC metrics and survival analyses. Results CCT5 was significantly overexpressed in tumor tissues and primarily localized to malignant and cycling cells. High CCT5 expression correlated with poor prognosis in multiple cancers and was enriched in oncogenic, cell cycle, and DNA damage repair pathways. CCT5 expression was positively associated with mRNAsi, mDNAsi, and CytoTRACE scores, indicating a role in stemness maintenance. Furthermore, CCT5-high tumors exhibited immune-cold phenotypes, with reduced TILs and CD8⁺ T cell activity. The CCT5.Sig model, based on genes co-expressed with CCT5, achieved superior predictive accuracy for ICB response (AUC = 0.82 in validation and 0.76 in independent testing), outperforming existing pan-cancer signatures. Conclusion This study reveals the multifaceted oncogenic roles of CCT5 and highlights its potential as a pan-cancer biomarker for prognosis and immunotherapy response. The machine learning-derived CCT5.Sig model provides a robust tool for patient stratification and may inform personalized immunotherapy strategies. Graphical abstract |
| format | Article |
| id | doaj-art-e0e582b7760742549fbc4356fc48da2f |
| institution | OA Journals |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-e0e582b7760742549fbc4356fc48da2f2025-08-20T02:06:27ZengSpringerCancer Immunology, Immunotherapy1432-08512025-05-0174712110.1007/s00262-025-04071-7Chaperonin containing TCP1 subunit 5 as a novel pan-cancer prognostic biomarker for tumor stemness and immunotherapy response: insights from multi-omics data, integrated machine learning, and experimental validationJiajun Li0Nuo Xu1Leyin Hu2Jiayue Xu3Yifan Huang4Deqi Wang5Feng Chen6Yi Wang7Jiani Jiang8Yanggang Hong9Huajun Ye10The Second School of Clinical Medicine, Wenzhou Medical UniversityState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute and Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Pathology, Zhejiang Cancer HospitalThe Second School of Clinical Medicine, Wenzhou Medical UniversityThe Second School of Clinical Medicine, Wenzhou Medical UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Wenzhou Medical UniversityThe Second School of Clinical Medicine, Wenzhou Medical UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Wenzhou Medical UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Wenzhou Medical UniversityThe Second School of Clinical Medicine, Wenzhou Medical UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Wenzhou Medical UniversityAbstract Background Chaperonin containing TCP1 subunit 5 (CCT5), a vital component of the molecular chaperonin complex, has been implicated in tumorigenesis, cancer stemness maintenance, and therapeutic resistance. Nevertheless, its comprehensive roles in pan-cancer progression, underlying biological functions, and potential as a predictor of immunotherapy response remains poorly understood. Methods We performed a comprehensive multi-omics pan-cancer analysis of CCT5 across 33 cancer types, integrating bulk RNA-seq, single-cell RNA-seq (scRNA-seq), and spatial transcriptomics data. CCT5 expression patterns, prognostic relevance, stemness association, and immune microenvironment relationships were evaluated. A novel CCT5-based signature (CCT5.Sig) was developed using machine learning on 23 immune checkpoint blockade (ICB) cohorts (n = 1394) spanning eight cancer types. Model performance was assessed using AUC metrics and survival analyses. Results CCT5 was significantly overexpressed in tumor tissues and primarily localized to malignant and cycling cells. High CCT5 expression correlated with poor prognosis in multiple cancers and was enriched in oncogenic, cell cycle, and DNA damage repair pathways. CCT5 expression was positively associated with mRNAsi, mDNAsi, and CytoTRACE scores, indicating a role in stemness maintenance. Furthermore, CCT5-high tumors exhibited immune-cold phenotypes, with reduced TILs and CD8⁺ T cell activity. The CCT5.Sig model, based on genes co-expressed with CCT5, achieved superior predictive accuracy for ICB response (AUC = 0.82 in validation and 0.76 in independent testing), outperforming existing pan-cancer signatures. Conclusion This study reveals the multifaceted oncogenic roles of CCT5 and highlights its potential as a pan-cancer biomarker for prognosis and immunotherapy response. The machine learning-derived CCT5.Sig model provides a robust tool for patient stratification and may inform personalized immunotherapy strategies. Graphical abstracthttps://doi.org/10.1007/s00262-025-04071-7CCT5Pan-cancerCancer stemnessTumor microenvironmentImmune checkpoint blockadeSingle-cell analysis |
| spellingShingle | Jiajun Li Nuo Xu Leyin Hu Jiayue Xu Yifan Huang Deqi Wang Feng Chen Yi Wang Jiani Jiang Yanggang Hong Huajun Ye Chaperonin containing TCP1 subunit 5 as a novel pan-cancer prognostic biomarker for tumor stemness and immunotherapy response: insights from multi-omics data, integrated machine learning, and experimental validation Cancer Immunology, Immunotherapy CCT5 Pan-cancer Cancer stemness Tumor microenvironment Immune checkpoint blockade Single-cell analysis |
| title | Chaperonin containing TCP1 subunit 5 as a novel pan-cancer prognostic biomarker for tumor stemness and immunotherapy response: insights from multi-omics data, integrated machine learning, and experimental validation |
| title_full | Chaperonin containing TCP1 subunit 5 as a novel pan-cancer prognostic biomarker for tumor stemness and immunotherapy response: insights from multi-omics data, integrated machine learning, and experimental validation |
| title_fullStr | Chaperonin containing TCP1 subunit 5 as a novel pan-cancer prognostic biomarker for tumor stemness and immunotherapy response: insights from multi-omics data, integrated machine learning, and experimental validation |
| title_full_unstemmed | Chaperonin containing TCP1 subunit 5 as a novel pan-cancer prognostic biomarker for tumor stemness and immunotherapy response: insights from multi-omics data, integrated machine learning, and experimental validation |
| title_short | Chaperonin containing TCP1 subunit 5 as a novel pan-cancer prognostic biomarker for tumor stemness and immunotherapy response: insights from multi-omics data, integrated machine learning, and experimental validation |
| title_sort | chaperonin containing tcp1 subunit 5 as a novel pan cancer prognostic biomarker for tumor stemness and immunotherapy response insights from multi omics data integrated machine learning and experimental validation |
| topic | CCT5 Pan-cancer Cancer stemness Tumor microenvironment Immune checkpoint blockade Single-cell analysis |
| url | https://doi.org/10.1007/s00262-025-04071-7 |
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