Comprehensive analysis of α2,3-sialyltransferases as prognostic biomarkers and immunotherapy targets in kidney renal clear cell carcinoma
Abstract Kidney renal clear cell carcinoma (KIRC), a therapy-resistant aggressive kidney cancer, exhibits resistance to immune checkpoint inhibitors. Altered sialylation is involved in tumor development, affecting immune microenvironment dynamics. In the study, through systematic bioinformatics anal...
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2025-02-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03640-1 |
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| author | Yuli Jian Kangkang Yang Jinjing Li Ling Tang Guang Zeng Xiaoxin Sun Xiao Yu Abdullah Al-danakh Qiwei Chen Deyong Yang Shujing Wang |
| author_facet | Yuli Jian Kangkang Yang Jinjing Li Ling Tang Guang Zeng Xiaoxin Sun Xiao Yu Abdullah Al-danakh Qiwei Chen Deyong Yang Shujing Wang |
| author_sort | Yuli Jian |
| collection | DOAJ |
| description | Abstract Kidney renal clear cell carcinoma (KIRC), a therapy-resistant aggressive kidney cancer, exhibits resistance to immune checkpoint inhibitors. Altered sialylation is involved in tumor development, affecting immune microenvironment dynamics. In the study, through systematic bioinformatics analysis and experimental verification, we demonstrated that ST3Gal5 expression was elevated in tumor tissues of KIRC patients, correlating with poor prognosis, and ST3Gal1 was downregulated and associated with a better prognosis. Immunohistochemistry analysis confirmed the expression patterns of ST3Gal1 and ST3Gal5 in 30 KIRC patients. Furthermore, KIRC patients were stratified into two clusters based on ST3Gal1 and ST3Gal5 levels using consensus clustering to investigate their roles in KIRC tumorigenesis, immune characteristics and treatment sensitivity. KIRC patients in Cluster 2, characterized by increased ST3Gal5 and downregulated ST3Gal1 expression, exhibited increased expression of immune checkpoints, immune cell infiltration, immune escape scores, and worse prognosis. Knockdown of ST3Gal5 in KIRC cell lines (786-O and 769-P) resulted in reduced tumor proliferation, migration, and invasion in vivo and in vitro. Together, the dysregulation of sialyltransferases (ST3Gal1 and ST3Gal5) in KIRC influences tumorigenesis and immune responses. These findings underscore the potential of ST3Gal1 and ST3Gal5 as prognostic factors and immunotherapy targets for KIRC. |
| format | Article |
| id | doaj-art-65811c0e4e13466480033f71b90a72fb |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-65811c0e4e13466480033f71b90a72fb2025-02-09T12:55:25ZengBMCCancer Cell International1475-28672025-02-0125111310.1186/s12935-025-03640-1Comprehensive analysis of α2,3-sialyltransferases as prognostic biomarkers and immunotherapy targets in kidney renal clear cell carcinomaYuli Jian0Kangkang Yang1Jinjing Li2Ling Tang3Guang Zeng4Xiaoxin Sun5Xiao Yu6Abdullah Al-danakh7Qiwei Chen8Deyong Yang9Shujing Wang10Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian Medical UniversityLiaoning Provincial Core Lab of Glycobiology and Glycoengineering, College of Basic Medical Sciences, Dalian Medical UniversityLiaoning Provincial Core Lab of Glycobiology and Glycoengineering, College of Basic Medical Sciences, Dalian Medical UniversityLiaoning Provincial Core Lab of Glycobiology and Glycoengineering, College of Basic Medical Sciences, Dalian Medical UniversityInstitute (College) of Integrative Medicine, Dalian Medical UniversityLiaoning Provincial Core Lab of Glycobiology and Glycoengineering, College of Basic Medical Sciences, Dalian Medical UniversityDepartment of Pathology and Forensic Medicine, College of Basic Medical Sciences, Dalian Medical UniversityDepartment of Urology, First Affiliated Hospital of Dalian Medical University, Dalian Medical UniversityDepartment of Urology, First Affiliated Hospital of Dalian Medical University, Dalian Medical UniversityDepartment of Urology, First Affiliated Hospital of Dalian Medical University, Dalian Medical UniversityLiaoning Provincial Core Lab of Glycobiology and Glycoengineering, College of Basic Medical Sciences, Dalian Medical UniversityAbstract Kidney renal clear cell carcinoma (KIRC), a therapy-resistant aggressive kidney cancer, exhibits resistance to immune checkpoint inhibitors. Altered sialylation is involved in tumor development, affecting immune microenvironment dynamics. In the study, through systematic bioinformatics analysis and experimental verification, we demonstrated that ST3Gal5 expression was elevated in tumor tissues of KIRC patients, correlating with poor prognosis, and ST3Gal1 was downregulated and associated with a better prognosis. Immunohistochemistry analysis confirmed the expression patterns of ST3Gal1 and ST3Gal5 in 30 KIRC patients. Furthermore, KIRC patients were stratified into two clusters based on ST3Gal1 and ST3Gal5 levels using consensus clustering to investigate their roles in KIRC tumorigenesis, immune characteristics and treatment sensitivity. KIRC patients in Cluster 2, characterized by increased ST3Gal5 and downregulated ST3Gal1 expression, exhibited increased expression of immune checkpoints, immune cell infiltration, immune escape scores, and worse prognosis. Knockdown of ST3Gal5 in KIRC cell lines (786-O and 769-P) resulted in reduced tumor proliferation, migration, and invasion in vivo and in vitro. Together, the dysregulation of sialyltransferases (ST3Gal1 and ST3Gal5) in KIRC influences tumorigenesis and immune responses. These findings underscore the potential of ST3Gal1 and ST3Gal5 as prognostic factors and immunotherapy targets for KIRC.https://doi.org/10.1186/s12935-025-03640-1Kidney renal clear cell carcinomaST3GalsTumor immune microenvironmentImmunotherapyPrognostic biomarkers |
| spellingShingle | Yuli Jian Kangkang Yang Jinjing Li Ling Tang Guang Zeng Xiaoxin Sun Xiao Yu Abdullah Al-danakh Qiwei Chen Deyong Yang Shujing Wang Comprehensive analysis of α2,3-sialyltransferases as prognostic biomarkers and immunotherapy targets in kidney renal clear cell carcinoma Cancer Cell International Kidney renal clear cell carcinoma ST3Gals Tumor immune microenvironment Immunotherapy Prognostic biomarkers |
| title | Comprehensive analysis of α2,3-sialyltransferases as prognostic biomarkers and immunotherapy targets in kidney renal clear cell carcinoma |
| title_full | Comprehensive analysis of α2,3-sialyltransferases as prognostic biomarkers and immunotherapy targets in kidney renal clear cell carcinoma |
| title_fullStr | Comprehensive analysis of α2,3-sialyltransferases as prognostic biomarkers and immunotherapy targets in kidney renal clear cell carcinoma |
| title_full_unstemmed | Comprehensive analysis of α2,3-sialyltransferases as prognostic biomarkers and immunotherapy targets in kidney renal clear cell carcinoma |
| title_short | Comprehensive analysis of α2,3-sialyltransferases as prognostic biomarkers and immunotherapy targets in kidney renal clear cell carcinoma |
| title_sort | comprehensive analysis of α2 3 sialyltransferases as prognostic biomarkers and immunotherapy targets in kidney renal clear cell carcinoma |
| topic | Kidney renal clear cell carcinoma ST3Gals Tumor immune microenvironment Immunotherapy Prognostic biomarkers |
| url | https://doi.org/10.1186/s12935-025-03640-1 |
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