Integrative analysis of m6A-SNPs and single-cell RNA sequencing reveals key drivers of endocrine combined with CDK4/6 inhibitor therapy resistance in ER+ breast cancer DOI Creative Commons

Ruijie Ming,

Han Zhang, Huan Wu

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 15, 2025

Background Endocrine therapy combined with CDK4/6 inhibitors remains a standard treatment for ER+ breast cancer, yet resistance is prevalent challenge. This study explores the role of N6-methyladenosine (m6A) modifications, influenced by m6A-SNPs, in shaping resistance, utilizing single-cell RNA sequencing to delineate underlying molecular mechanisms. Methods We integrated genome-wide association data transcriptomic profiles from cancer patients, focusing on differences between resistant and sensitive responses inhibitors. m6A-SNPs were identified analyzed their impact gene expression interactions RNA-binding proteins, particular focus roles within key cellular pathways. Results The crucial associated resistance. Notably, changes FILIP1L TOM1L1, related these SNPs, mapped using pseudotime trajectory analysis, which traced evolution states. TOM1L1 exhibited dynamic along trajectory, correlating significant shifts cell fate decisions. These findings underscore potential as mediators development particularly through involvement PI3K-Akt Wnt signaling pathways, critical progression drug Conclusion Our emphasize importance influencing cancer. regulation developmental tumor cells sensitivity provides insights into complexity results pave way developing targeted therapies that modify m6A-driven offering new strategies counteract improve patient outcomes.

Language: Английский

5-Methylcytosine methylation predicts cervical cancer prognosis, shaping immune cell infiltration DOI Creative Commons

Luyang Su,

Ren Xu,

Yanan Ren

et al.

Journal of International Medical Research, Journal Year: 2025, Volume and Issue: 53(4)

Published: April 1, 2025

BackgroundEpigenetics, encompassing DNA and RNA modifications, has emerged as a prominent area of research in the post-genomic era. Numerous studies have elucidated impact epigenetics on tumor regulation. However, methylation patterns 5-methylcytosine cervical cancer well its role microenvironment immunotherapy remain poorly understood.MethodsUtilizing comprehensive dataset samples from 306 patients with The Cancer Genome Atlas Gene Expression Omnibus repositories, we conducted an in-depth analysis to evaluate potential association between modification infiltration cells within microenvironment, taking into account 11 regulators modification. Subsequently, employed stepwise regression Least Absolute Shrinkage Selection Operator Cox quantify squamous cell carcinoma endocervical adenocarcinoma, yielding score. Our study explored link score clinical characteristics prognostic outcomes adenocarcinoma.ResultsA revealed two distinct patterns, henceforth labeled clusters A B. These exhibited immunological profiles biological attributes, cluster exhibiting higher degree immune infiltration. Utilizing univariate analysis, identified 367 genes regulated by that were significantly correlated patient prognosis. This further stratified three genomic subtypes. Survival analyses indicated belonging gene C more favorable survival than those Intriguingly, most regulatory factors had expression levels B A. set enrichment single sample elevated B, indicating stronger response this cluster. feature was utilized determine pattern cancer, revealing low scores better rates, whereas high increased mutation frequencies treatment responses.ConclusionsThis underscores key cancer. Analysis these will deepen our understanding paving way for development refined effective strategies.

Language: Английский

Citations

0

Integrative analysis of m6A-SNPs and single-cell RNA sequencing reveals key drivers of endocrine combined with CDK4/6 inhibitor therapy resistance in ER+ breast cancer DOI Creative Commons

Ruijie Ming,

Han Zhang, Huan Wu

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 15, 2025

Background Endocrine therapy combined with CDK4/6 inhibitors remains a standard treatment for ER+ breast cancer, yet resistance is prevalent challenge. This study explores the role of N6-methyladenosine (m6A) modifications, influenced by m6A-SNPs, in shaping resistance, utilizing single-cell RNA sequencing to delineate underlying molecular mechanisms. Methods We integrated genome-wide association data transcriptomic profiles from cancer patients, focusing on differences between resistant and sensitive responses inhibitors. m6A-SNPs were identified analyzed their impact gene expression interactions RNA-binding proteins, particular focus roles within key cellular pathways. Results The crucial associated resistance. Notably, changes FILIP1L TOM1L1, related these SNPs, mapped using pseudotime trajectory analysis, which traced evolution states. TOM1L1 exhibited dynamic along trajectory, correlating significant shifts cell fate decisions. These findings underscore potential as mediators development particularly through involvement PI3K-Akt Wnt signaling pathways, critical progression drug Conclusion Our emphasize importance influencing cancer. regulation developmental tumor cells sensitivity provides insights into complexity results pave way developing targeted therapies that modify m6A-driven offering new strategies counteract improve patient outcomes.

Language: Английский

Citations

0