Takeshita Takashi, Yan Li, Peng Xuan, Kimbung Siker, Hatschek Thomas, Hedenfalk Ingrid A, Rashid Omar M, Takabe Kazuaki
Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center Buffalo, NY, USA.
Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center Buffalo, NY, USA.
Am J Cancer Res. 2020 Aug 1;10(8):2555-2569. eCollection 2020.
Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) has been proposed as a surrogate endpoint for the prediction of long-term survival in breast cancer (BC); however, an increased pCR rate has not clearly correlated with improved survival. We hypothesized that some transcriptomic and functional pathway features correlate with survival after pCR in BC. We utilized 2 published NAC cohorts, 105 women with gene expression data before, "Baseline", and that changed during NAC, "Delta", and TCGA database with 1068 BC patients to investigate the relationship between the efficacy of NAC and survival utilizing differentially expressed-mRNAs, construction and analysis of the mRNA-hub gene network, and functional pathway analysis. In mRNA expression profiling, was a gene involved in survival after pCR in Baseline and was a gene involved in recurrence after pCR in Delta. In functional pathway analysis, we found multiple pathways involved in survival after pCR. In mRNA-hub gene analysis, , , , and were related to recurrence in BC patients with pCR due to NAC. , , , , and may play a significant role in survival for patients with pCR. Interestingly, high , , , and , and low , , and expressing tumors have significantly worse overall survival in TCGA BC cohort. We demonstrated the genes and functional pathway features associated with pCR and survival utilizing the bioinformatics approach to public BC cohorts. Some genes involved in recurrence after pCR due to NAC also served as prognostic factors in primary BC.
新辅助化疗(NAC)后的病理完全缓解(pCR)已被提议作为预测乳腺癌(BC)长期生存的替代终点;然而,pCR率的提高与生存率的改善并未明确相关。我们假设一些转录组和功能通路特征与BC患者pCR后的生存相关。我们利用2个已发表的NAC队列、105名在NAC前有基因表达数据(“基线”)以及在NAC期间基因表达发生变化(“Delta”)的女性,以及有1068例BC患者的TCGA数据库,通过差异表达mRNA、mRNA枢纽基因网络的构建和分析以及功能通路分析来研究NAC疗效与生存之间的关系。在mRNA表达谱分析中, 是基线中与pCR后生存相关的基因, 是Delta中与pCR后复发相关的基因。在功能通路分析中,我们发现多个与pCR后生存相关的通路。在mRNA枢纽基因分析中, 、 、 、 与因NAC导致pCR的BC患者的复发相关。 、 、 、 、 可能在pCR患者的生存中起重要作用。有趣的是,在TCGA BC队列中,高表达 、 、 、 以及低表达 、 、 的肿瘤患者总生存期明显更差。我们利用生物信息学方法对公开的BC队列进行分析,展示了与pCR和生存相关的基因及功能通路特征。一些因NAC导致pCR后复发相关的基因在原发性BC中也可作为预后因素。