UNASSIGNED:先前的研究表明,肿瘤内异质性(ITH)与不良的临床结果有关,并被认为是化疗和放疗耐药的机制。
UNASSIGNED:我们旨在确定ITH如何影响乳腺癌(BC)对药物治疗的反应。
UNASSIGNED:我们使用TCGA数据库中BC患者的突变等位基因肿瘤异质性(MATH)数据评估了ITH。
UNASSIGNED:该研究从TCGA数据库中纳入了515例接受化疗的BC患者,这些患者有生存数据,全外显子组测序,和全基因组转录组测序。此外,399名MSK-BRCA队列患者接受化疗。
UNASSIGNED:所有统计分析均使用R进行。所有比较均使用双侧Mann-Whitney检验进行,皮尔森卡方检验,还有Kruskal-Wallis测试.统计学显著性定义为P值小于0.05(*P<0.05)。使用R中的生存包进行分析。
UNASSIGNED:对接受辅助化疗的515例BC患者进行了其他分析。在多变量分析中,MATH与总生存期(OS)相关(风险比(HR),1.432;95%置信区间,1.073-1.913;P=0.015)。途径富集和免疫细胞分析显示,低MATH组24种不同类型免疫细胞的浸润明显高于高MATH组。
UNASSIGNED:数学得分低的个体比数学得分高的个体具有更长的OS。在MATH评分较低的乳腺癌患者中,免疫反应显着增强。
UNASSIGNED: Previous studies have shown that intratumoral heterogeneity (ITH) is associated with poor clinical outcomes and is thought to be a mechanism of resistance to chemotherapy and radiotherapy.
UNASSIGNED: We aimed to determine how ITH affects the response to drug therapy in breast cancer (BC).
UNASSIGNED: We assessed ITH using mutated allele tumor heterogeneity (MATH) data from BC patients in the TCGA database.
UNASSIGNED: The study enrolled 515 patients with BC treated with chemotherapy from the TCGA database who had available data on survival, whole-exome sequencing, and genome-wide transcriptome sequencing. Additionally, 399 MSK-BRCA cohort patients were treated with chemotherapy.
UNASSIGNED: All statistical analyses were conducted using R. All comparisons were made using the two-sided Mann-Whitney test, Pearson\'s Chi-squared test, and the Kruskal-Wallis test. Statistical significance was defined as P values less than 0.05 (*P < 0.05). The survival package in R was used to conduct the analysis.
UNASSIGNED: Additional analysis was performed on 515 BC patients receiving adjuvant chemotherapy.
MATH was associated with overall survival (OS) in multivariate analysis (hazard ratio (HR), 1.432; 95% confidence interval, 1.073-1.913; P = 0.015). Pathway enrichment and immune cell analysis revealed that the low
MATH group had significantly higher infiltration of 24 different types of immune cells than the high
MATH group.
UNASSIGNED: Individuals with low
MATH scores had a longer OS than those with high
MATH scores. Immune responses were significantly enhanced in breast cancer patients with low
MATH scores.