Identification and validation of the role of ZNF281 in 5-fluorouracil chemotherapy of gastric cancer.
Stomach Neoplasms
/ drug therapy
Fluorouracil
/ therapeutic use
Humans
Prognosis
Wnt Signaling Pathway
Antimetabolites, Antineoplastic
/ therapeutic use
Cell Proliferation
Cell Line, Tumor
Tumor Microenvironment
Drug Resistance, Neoplasm
Apoptosis
/ drug effects
Repressor Proteins
/ genetics
Female
Gene Expression Regulation, Neoplastic
Male
Biomarkers, Tumor
/ metabolism
5-fluorouracil
DNA repair
Gastric cancer
Wnt/β-catenin pathway
ZNF281
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
16 Jun 2024
16 Jun 2024
Historique:
received:
15
04
2024
accepted:
05
06
2024
medline:
17
6
2024
pubmed:
17
6
2024
entrez:
16
6
2024
Statut:
epublish
Résumé
The early diagnosis of gastric cancer (GC) and overcoming chemotherapy resistance is challenging. The aberrant expression of zinc finger protein 281 (ZNF281) and the over-activation of the Wnt/β-catenin pathway are oncogenic factors and confer tumor chemoresistance. ZNF281 modulates the Wnt/β-catenin pathway to influence malignant tumor behavior. However, the role of ZNF281 in GC chemotherapy and the relationship with the Wnt/β-catenin pathway have not been elucidated by researchers. We explored differences in ZNF281 expression in Pan-cancer and normal tissues, the effect of its expression on prognosis of patients treated with 5-fluorouracil (5-FU). Cox regression was utilized to determine whether ZNF281 is an independent prognostic factor. Enrichment analysis was performed to explore the mechanism underlying ZNF281's role in 5-FU treatment. We assessed the relationship between ZNF281 and the tumour microenvironment (TME) and combined bulk-RNA and single-cell RNA data to analyse the relationship between ZNF281 and immune infiltration. In vitro experiments verified the effects of ZNF281 knockdown on proliferation, invasion, migration, apoptosis, DNA damage of GC cells with 5-FU treated and the Wnt/β-catenin pathway proteins. ZNF281 was highly expressed in seven cancers and correlates with the prognosis. It is an independent prognostic factor in 5-FU treatment. ZNF281 correlates with TME score, CD8T cell abundance. ZNF281 is primarily associated with DNA repair and the Wnt/β-catenin pathway. ZNF281 knockdown enhanced the effect of 5-FU on phenotypes of GC cells. We identified and verified ZNF281 as one of the potential influencing factors of 5-FU treatment in GC and may be associated with the Wnt/β-catenin pathway. Low ZNF281 may contribute to improved 5-FU sensitivity in GC patients.
Sections du résumé
BACKGROUND
BACKGROUND
The early diagnosis of gastric cancer (GC) and overcoming chemotherapy resistance is challenging. The aberrant expression of zinc finger protein 281 (ZNF281) and the over-activation of the Wnt/β-catenin pathway are oncogenic factors and confer tumor chemoresistance. ZNF281 modulates the Wnt/β-catenin pathway to influence malignant tumor behavior. However, the role of ZNF281 in GC chemotherapy and the relationship with the Wnt/β-catenin pathway have not been elucidated by researchers.
METHODS
METHODS
We explored differences in ZNF281 expression in Pan-cancer and normal tissues, the effect of its expression on prognosis of patients treated with 5-fluorouracil (5-FU). Cox regression was utilized to determine whether ZNF281 is an independent prognostic factor. Enrichment analysis was performed to explore the mechanism underlying ZNF281's role in 5-FU treatment. We assessed the relationship between ZNF281 and the tumour microenvironment (TME) and combined bulk-RNA and single-cell RNA data to analyse the relationship between ZNF281 and immune infiltration. In vitro experiments verified the effects of ZNF281 knockdown on proliferation, invasion, migration, apoptosis, DNA damage of GC cells with 5-FU treated and the Wnt/β-catenin pathway proteins.
RESULTS
RESULTS
ZNF281 was highly expressed in seven cancers and correlates with the prognosis. It is an independent prognostic factor in 5-FU treatment. ZNF281 correlates with TME score, CD8T cell abundance. ZNF281 is primarily associated with DNA repair and the Wnt/β-catenin pathway. ZNF281 knockdown enhanced the effect of 5-FU on phenotypes of GC cells.
CONCLUSION
CONCLUSIONS
We identified and verified ZNF281 as one of the potential influencing factors of 5-FU treatment in GC and may be associated with the Wnt/β-catenin pathway. Low ZNF281 may contribute to improved 5-FU sensitivity in GC patients.
Identifiants
pubmed: 38880820
doi: 10.1007/s00432-024-05838-8
pii: 10.1007/s00432-024-05838-8
doi:
Substances chimiques
Fluorouracil
U3P01618RT
Antimetabolites, Antineoplastic
0
Repressor Proteins
0
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
307Subventions
Organisme : Ruida Pharmaceutical Clinical Medicine Postgraduate Education Innovation Training Base Project of Henan University
ID : SYLJD2022009
Organisme : Program for Innovative Research Team (in Science and Technology) in University of Henan Province
ID : 24IRTSTHN041
Informations de copyright
© 2024. The Author(s).
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