■这项研究的目的是根据染色质调节因子相关基因鉴定乳腺癌的分子亚型。
■癌症基因组图谱-乳腺癌队列的RNA测序数据来自官方网站,而单细胞数据是从基因表达综合数据库(GSE176078)下载的。使用乳腺癌国际联盟的分子分类学数据集进行验证。此外,免疫特性,肿瘤干性,异质性,并对这些分子亚型的临床特征进行分析。使用定量实时聚合酶链反应(qRT-PCR)和细胞计数试剂盒-8(CCK8)测定在体外检查染色质调节剂与化疗抗性之间的相关性。
■这项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,京都基因和基因组百科全书,和蛋白质-蛋白质相互作用分析表明,差异表达的基因与疾病过程有关,如有丝分裂核分裂,染色体分离,凝聚染色体,和特定的染色体区域。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,肿瘤突变负担,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RNA表达的干性评分,基于DNA甲基化的干性评分,和表观遗传调节的基于DNA甲基化的干性评分)在三种亚型之间显着变化。此外,西方印迹,qRT-PCR,CCK8检测表明,ASCL1的表达与乳腺癌化疗耐药呈正相关。
■这项研究根据染色质调节剂确定了乳腺癌的亚型,并分析了其临床特征,基因突变状态,免疫表型,和药物敏感性。这项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。
UNASSIGNED: The aim of this study was to identify the molecular subtypes of breast cancer based on chromatin regulator-related genes.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.