Identification and validation of sialyltransferase ST3Gal5 in bladder cancer through bioinformatics and experimental analysis.
Bladder cancer
Immunotherapy
Prognostic biomarker
ST3Gal5
Tumorigenesis
Journal
International immunopharmacology
ISSN: 1878-1705
Titre abrégé: Int Immunopharmacol
Pays: Netherlands
ID NLM: 100965259
Informations de publication
Date de publication:
02 Jul 2024
02 Jul 2024
Historique:
received:
21
03
2024
revised:
12
06
2024
accepted:
24
06
2024
medline:
3
7
2024
pubmed:
3
7
2024
entrez:
3
7
2024
Statut:
aheadofprint
Résumé
Bladder cancer (BLCA) is one of the top ten most common cancers in the world. Aberrant sialylation is a common feature in tumorigenesis and tumor immunity. This study seeks to explore the potential impact of sialyltransferase ST3Gal5 on BLCA. Initially, glycosyltransferase-related DEGs (GRDEGs) were identified using multiple bioinformatics approaches in TCGA-BLCA cohort and validated using GEO databases. Clinical prognosis integration facilitated the determination of ST3Gal5 as an independent prognostic factor in BLCA, employing univariate and multivariate Cox regression analyses. Immune cell infiltration was assessed via CIBERSORT and ssGSEA analyses, while HLA and immune checkpoint genes' levels, along with drug sensitivity, were evaluated in low- and high-ST3Gal5 groups. The TIDE and IPS scores were used to gauge the immune checkpoint blockade (ICB) response. Furthermore, functional experiments, both in vivo and in vitro, were conducted to elucidate the biological roles of ST3Gal5. In agreement with bioinformatics findings, ST3Gal5 expression was down-regulated in BLCA tissues and cells, correlating with poorer prognostic outcomes. The StromalScore, ImmuneScore, and ESTIMATEScore were significantly elevated in low-ST3Gal5 group. Moreover, the levels of HLA and immune checkpoint genes were upregulated in low-ST3Gal5 group. Down-regulated ST3Gal5 promoted the proliferation, migration, and invasion of BLCA cells in vivo and in vitro. Our findings demonstrated that low ST3Gal5 level promoted tumorigenesis and progression of BLCA, implying its potential as a predictive biomarker and therapeutic target.
Sections du résumé
BACKGROUND
BACKGROUND
Bladder cancer (BLCA) is one of the top ten most common cancers in the world. Aberrant sialylation is a common feature in tumorigenesis and tumor immunity. This study seeks to explore the potential impact of sialyltransferase ST3Gal5 on BLCA.
METHODS
METHODS
Initially, glycosyltransferase-related DEGs (GRDEGs) were identified using multiple bioinformatics approaches in TCGA-BLCA cohort and validated using GEO databases. Clinical prognosis integration facilitated the determination of ST3Gal5 as an independent prognostic factor in BLCA, employing univariate and multivariate Cox regression analyses. Immune cell infiltration was assessed via CIBERSORT and ssGSEA analyses, while HLA and immune checkpoint genes' levels, along with drug sensitivity, were evaluated in low- and high-ST3Gal5 groups. The TIDE and IPS scores were used to gauge the immune checkpoint blockade (ICB) response. Furthermore, functional experiments, both in vivo and in vitro, were conducted to elucidate the biological roles of ST3Gal5.
RESULTS
RESULTS
In agreement with bioinformatics findings, ST3Gal5 expression was down-regulated in BLCA tissues and cells, correlating with poorer prognostic outcomes. The StromalScore, ImmuneScore, and ESTIMATEScore were significantly elevated in low-ST3Gal5 group. Moreover, the levels of HLA and immune checkpoint genes were upregulated in low-ST3Gal5 group. Down-regulated ST3Gal5 promoted the proliferation, migration, and invasion of BLCA cells in vivo and in vitro.
CONCLUSION
CONCLUSIONS
Our findings demonstrated that low ST3Gal5 level promoted tumorigenesis and progression of BLCA, implying its potential as a predictive biomarker and therapeutic target.
Identifiants
pubmed: 38959540
pii: S1567-5769(24)01090-7
doi: 10.1016/j.intimp.2024.112569
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112569Informations de copyright
Copyright © 2024 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.