A novel Senescence-Based prognostic model unveils tumor interactions and drug resistance in colorectal cancer.
Int Immunopharmacol
; 134: 112197, 2024 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-38733826
ABSTRACT
BACKGROUND:
In China, CRC incidence is escalating. The main hurdles are heterogeneity and drug resistance. This research delves into cellular senescence in CRC, aiming to devise a prognostic model and pinpoint mechanisms impacting drug resistance.METHODS:
Mendelian randomization (MR) analysis confirmed the association between CRC and cellular aging. The Cancer Genome Atlas (TCGA)-CRC data served as the training set, with GSE38832 and GSE39582 as validation sets. Various bioinformatics methods were employed to construct and validate a risk model. CRC cells with NADPH Oxidase 4 (NOX4) knockout were generated using CRISPR-Cas9 technology. Protein blotting and colony formation assays elucidated the role of NOX4 in CRC cell aging and drug resistance.RESULTS:
A prognostic model, derived from dataset analysis, uncovered a link between high-risk groups and cancer progression. Notable differences in the tumor microenvironment were observed between risk groups. Finally, NOX4 was found to be linked with aging and drug resistance in CRC.CONCLUSION:
This research presents a novel senescence-based CRC prognosis model. It identifies NOX4's role in CRC drug resistance, suggesting it is a potential treatment target.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Senescência Celular
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Resistencia a Medicamentos Antineoplásicos
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NADPH Oxidase 4
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Int Immunopharmacol
Ano de publicação:
2024
Tipo de documento:
Article