Identification of ST3GAL5 as a prognostic biomarker correlating with CD8+ T cell exhaustion in clear cell renal cell carcinoma

Aberrant sialylation is frequently observed in tumor development, but which sialyltransferases are involved in this event are not well known. Herein, we performed comprehensive analyses on six ST3GAL family members, the α-2,3 sialyltransferases, in clear cell renal cell carcinoma (ccRCC) from public...

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Main Authors: Jiakuan Liu, Meiqian Li, Jiajun Wu, Qi Qi, Yang Li, Simei Wang, Shengjie Liang, Yuqing Zhang, Zhitao Zhu, Ruimin Huang, Jun Yan, Rujian Zhu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.979605/full
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author Jiakuan Liu
Jiakuan Liu
Meiqian Li
Meiqian Li
Jiajun Wu
Qi Qi
Yang Li
Simei Wang
Simei Wang
Shengjie Liang
Yuqing Zhang
Zhitao Zhu
Ruimin Huang
Ruimin Huang
Jun Yan
Jun Yan
Rujian Zhu
author_facet Jiakuan Liu
Jiakuan Liu
Meiqian Li
Meiqian Li
Jiajun Wu
Qi Qi
Yang Li
Simei Wang
Simei Wang
Shengjie Liang
Yuqing Zhang
Zhitao Zhu
Ruimin Huang
Ruimin Huang
Jun Yan
Jun Yan
Rujian Zhu
author_sort Jiakuan Liu
collection DOAJ
description Aberrant sialylation is frequently observed in tumor development, but which sialyltransferases are involved in this event are not well known. Herein, we performed comprehensive analyses on six ST3GAL family members, the α-2,3 sialyltransferases, in clear cell renal cell carcinoma (ccRCC) from public datasets. Only ST3GAL5 was consistently and significantly overexpressed in ccRCC (n = 791 in total), compared with normal kidney tissues. Its overexpression was positively correlated with tumor stage, grade, and the poor prognosis in ccRCC patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated the involvement of ST3GAL5 in tumor immunoregulation. Then we revealed that ST3GAL5 expression showed a positive correlation with CD8+ T cell infiltration, using multiple tools on TIMER2.0 web server. Notably, ST3GAL5 overexpression was further identified to be associated with expression signature of CD8+ T cell exhaustion in ccRCC samples from three datasets (n = 867 in total; r > 0.3, p < 0.001). In our own ccRCC cohort (n = 45), immunohistochemistry and immunofluorescence staining confirmed that ST3GAL5 overexpression was accompanied by high CD8+ T cell infiltration with the increased exhaustion markers. Altogether, ST3GAL5 as a promising prognostic biomarker with CD8+ T cell exhaustion in ccRCC is indicated.
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spelling doaj.art-8a4d49da0e624fde8c1158eb974371ef2022-12-22T03:47:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.979605979605Identification of ST3GAL5 as a prognostic biomarker correlating with CD8+ T cell exhaustion in clear cell renal cell carcinomaJiakuan Liu0Jiakuan Liu1Meiqian Li2Meiqian Li3Jiajun Wu4Qi Qi5Yang Li6Simei Wang7Simei Wang8Shengjie Liang9Yuqing Zhang10Zhitao Zhu11Ruimin Huang12Ruimin Huang13Jun Yan14Jun Yan15Rujian Zhu16Department of Urology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, ChinaDepartment of Laboratory Animal Science, Fudan University, Shanghai, ChinaDepartment of Urology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, ChinaModel Animal Research Center of Nanjing University, Nanjing University, Jiangsu, ChinaDepartment of Laboratory Animal Science, Fudan University, Shanghai, ChinaDepartment of Laboratory Animal Science, Fudan University, Shanghai, ChinaDepartment of Urology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, ChinaShanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaDepartment of Urology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, ChinaDepartment of Urology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, ChinaDepartment of Laboratory Animal Science, Fudan University, Shanghai, ChinaShanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaDepartment of Urology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, ChinaDepartment of Laboratory Animal Science, Fudan University, Shanghai, ChinaDepartment of Urology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, ChinaAberrant sialylation is frequently observed in tumor development, but which sialyltransferases are involved in this event are not well known. Herein, we performed comprehensive analyses on six ST3GAL family members, the α-2,3 sialyltransferases, in clear cell renal cell carcinoma (ccRCC) from public datasets. Only ST3GAL5 was consistently and significantly overexpressed in ccRCC (n = 791 in total), compared with normal kidney tissues. Its overexpression was positively correlated with tumor stage, grade, and the poor prognosis in ccRCC patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated the involvement of ST3GAL5 in tumor immunoregulation. Then we revealed that ST3GAL5 expression showed a positive correlation with CD8+ T cell infiltration, using multiple tools on TIMER2.0 web server. Notably, ST3GAL5 overexpression was further identified to be associated with expression signature of CD8+ T cell exhaustion in ccRCC samples from three datasets (n = 867 in total; r > 0.3, p < 0.001). In our own ccRCC cohort (n = 45), immunohistochemistry and immunofluorescence staining confirmed that ST3GAL5 overexpression was accompanied by high CD8+ T cell infiltration with the increased exhaustion markers. Altogether, ST3GAL5 as a promising prognostic biomarker with CD8+ T cell exhaustion in ccRCC is indicated.https://www.frontiersin.org/articles/10.3389/fimmu.2022.979605/fullsialylationclear cell renal cell carcinomaST3GAL5CD8+ T cell exhaustionprognostic biomarker
spellingShingle Jiakuan Liu
Jiakuan Liu
Meiqian Li
Meiqian Li
Jiajun Wu
Qi Qi
Yang Li
Simei Wang
Simei Wang
Shengjie Liang
Yuqing Zhang
Zhitao Zhu
Ruimin Huang
Ruimin Huang
Jun Yan
Jun Yan
Rujian Zhu
Identification of ST3GAL5 as a prognostic biomarker correlating with CD8+ T cell exhaustion in clear cell renal cell carcinoma
Frontiers in Immunology
sialylation
clear cell renal cell carcinoma
ST3GAL5
CD8+ T cell exhaustion
prognostic biomarker
title Identification of ST3GAL5 as a prognostic biomarker correlating with CD8+ T cell exhaustion in clear cell renal cell carcinoma
title_full Identification of ST3GAL5 as a prognostic biomarker correlating with CD8+ T cell exhaustion in clear cell renal cell carcinoma
title_fullStr Identification of ST3GAL5 as a prognostic biomarker correlating with CD8+ T cell exhaustion in clear cell renal cell carcinoma
title_full_unstemmed Identification of ST3GAL5 as a prognostic biomarker correlating with CD8+ T cell exhaustion in clear cell renal cell carcinoma
title_short Identification of ST3GAL5 as a prognostic biomarker correlating with CD8+ T cell exhaustion in clear cell renal cell carcinoma
title_sort identification of st3gal5 as a prognostic biomarker correlating with cd8 t cell exhaustion in clear cell renal cell carcinoma
topic sialylation
clear cell renal cell carcinoma
ST3GAL5
CD8+ T cell exhaustion
prognostic biomarker
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.979605/full
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