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Identification of molecular subtypes based on chromatin regulator-related genes and experimental verification of the role of ASCL1 in conferring chemotherapy resistance to breast cancer.
Li, Yilun; Yang, Xiaolu; Geng, Cuizhi; Liu, Yunjiang; Tang, Tiantian; Zhang, Lina; Liu, Fei; Zhang, Meng; Hao, Jun; Ma, Li.
Afiliación
  • Li Y; Department of Breast Disease Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
  • Yang X; Department of Pathology, Hebei Medical University, Shijiazhuang, China.
  • Geng C; Department of Breast Disease Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
  • Liu Y; Department of Pathology, Hebei Medical University, Shijiazhuang, China.
  • Tang T; Department of Breast Disease Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
  • Zhang L; Department of Breast Disease Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
  • Liu F; Department of Breast Disease Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
  • Zhang M; Department of Breast Disease Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
  • Hao J; Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
  • Ma L; Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Front Immunol ; 15: 1390261, 2024.
Article en En | MEDLINE | ID: mdl-38726001
ABSTRACT

Objective:

The aim of this study was to identify the molecular subtypes of breast cancer based on chromatin regulator-related genes.

Methods:

The RNA sequencing data of The Cancer Genome Atlas-Breast Cancer cohort were obtained from the official website, while the single-cell data were downloaded from the Gene Expression Omnibus database (GSE176078). Validation was performed using the Molecular Taxonomy of Breast Cancer International Consortium dataset. Furthermore, the immune characteristics, tumor stemness, heterogeneity, and clinical characteristics of these molecular subtypes were analyzed. The correlation between chromatin regulators and chemotherapy resistance was examined in vitro using the quantitative real-time polymerase chain reaction (qRT-PCR) and Cell Counting Kit-8 (CCK8) assays.

Results:

This study identified three stable molecular subtypes with different prognostic and pathological features. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction analyses revealed that the differentially expressed genes were associated with disease processes, such as mitotic nuclear division, chromosome segregation, condensed chromosome, and specific chromosome region. The T stage and subtypes were correlated with the clinical features. Tumor heterogeneity (mutant-allele tumor heterogeneity, tumor mutational burden, purity, and homologous recombination deficiency) and tumor stemness (RNA expression-based stemness score, epigenetically regulated RNA expression-based stemness score, DNA methylation-based stemness score, and epigenetically regulated DNA methylation-based stemness score) significantly varied between the three subtypes. Furthermore, Western blotting, qRT-PCR, and CCK8 assays demonstrated that the expression of ASCL1 was positively correlated with chemotherapy resistance in breast cancer.

Conclusion:

This study identified the subtypes of breast cancer based on chromatin regulators and analyzed their clinical features, gene mutation status, immunophenotype, and drug sensitivity. The results of this study provide effective strategies for assessing clinical prognosis and developing personalized treatment strategies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Regulación Neoplásica de la Expresión Génica / Resistencia a Antineoplásicos / Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico Límite: Female / Humans Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Regulación Neoplásica de la Expresión Génica / Resistencia a Antineoplásicos / Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico Límite: Female / Humans Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza