Li Yang, Wang Maohua, Yang Siyuan, Kuang Licheng, Tao Xinling, Yang Jilan, Zhao Wentao, Zhang Ji
Department of Gastrointestinal Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, Yunnan, China.
The First Department of Breast Surgery, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, Yunnan, China.
J Cancer Res Ther. 2022 Sep;18(5):1268-1275. doi: 10.4103/jcrt.jcrt_1166_21.
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.
We aimed to determine how ITH affects the response to drug therapy in breast cancer (BC).
We assessed ITH using mutated allele tumor heterogeneity (MATH) data from BC patients in the TCGA database.
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.
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.
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.
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.
先前的研究表明，肿瘤内异质性（ITH）与不良临床结局相关，并且被认为是对化疗和放疗产生耐药性的一种机制。
我们旨在确定ITH如何影响乳腺癌（BC）对药物治疗的反应。
我们使用来自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ITH。
该研究纳入了TCGA数据库中515例接受化疗的BC患者，这些患者有生存、全外显子测序和全基因组转录组测序的可用数据。此外，399例MSK-BRCA队列患者接受了化疗。
所有统计分析均使用R进行。所有比较均使用双侧曼-惠特尼检验、皮尔逊卡方检验和克鲁斯卡尔-沃利斯检验。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。
对515例接受辅助化疗的BC患者进行了进一步分析。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）。通路富集和免疫细胞分析显示，低MATH组比高MATH组有24种不同类型免疫细胞的显著更高浸润。
MATH评分低的个体比MATH评分高的个体有更长的OS。MATH评分低的乳腺癌患者免疫反应显著增强。
