Department of Breast Disease Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Pathology, Hebei Medical University, Shijiazhuang, China.
Front Immunol. 2024 Apr 25;15:1390261. doi: 10.3389/fimmu.2024.1390261. eCollection 2024.
The aim of this study was to identify the molecular subtypes of breast cancer based on chromatin regulator-related genes.
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 using the quantitative real-time polymerase chain reaction (qRT-PCR) and Cell Counting Kit-8 (CCK8) assays.
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.
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.
本研究旨在基于染色质调控相关基因鉴定乳腺癌的分子亚型。
从官方网站获取癌症基因组图谱-乳腺癌队列的 RNA 测序数据，从基因表达综合数据库（GSE176078）下载单细胞数据。使用乳腺癌国际分子分类联盟数据集进行验证。此外，还分析了这些分子亚型的免疫特征、肿瘤干性、异质性和临床特征。使用实时定量聚合酶链反应（qRT-PCR）和细胞计数试剂盒-8（CCK8）检测染色质调节剂与化疗耐药性的相关性。
本研究确定了三种具有不同预后和病理特征的稳定分子亚型。基因本体论、京都基因与基因组百科全书和蛋白质-蛋白质相互作用分析表明，差异表达基因与疾病过程相关，如有丝分裂核分裂、染色体分离、浓缩染色体和特定染色体区域。T 分期和亚型与临床特征相关。肿瘤异质性（突变等位基因肿瘤异质性、肿瘤突变负荷、纯度和同源重组缺陷）和肿瘤干性（基于 RNA 表达的干性评分、基于表观遗传调控的 RNA 表达干性评分、基于 DNA 甲基化的干性评分和基于表观遗传调控的 DNA 甲基化的干性评分）在三种亚型之间存在显著差异。此外，Western blot、qRT-PCR 和 CCK8 检测表明，ASCL1 的表达与乳腺癌的化疗耐药性呈正相关。
本研究基于染色质调控因子鉴定了乳腺癌的亚型，并分析了它们的临床特征、基因突变状态、免疫表型和药物敏感性。本研究的结果为评估临床预后和制定个性化治疗策略提供了有效的策略。
