Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk 634009, Russia.
Biological Institute, National Research Tomsk State University, Tomsk 634050, Russia.
Int J Mol Sci. 2022 Nov 11;23(22):13906. doi: 10.3390/ijms232213906.
The assessment of molecular genetic landscape changes during NAC and the relationship between molecular signatures in residual tumors are promising approaches for identifying effective markers of outcome in breast cancer. The majority of the data in the literature present the relationship between the molecular genetic landscape and the response to NAC or are simply descriptive. The present study aimed to determine changes in expression profiles during NAC and assess the relationship between gene expression and the outcome of patients with luminal B HER2 breast cancer depending on distant hematogenous metastasis. The study included 39 patients with luminal B HER2-BC. The patients received 6-8 courses of NAC, and paired samples consisting of biopsy and surgical materials were analyzed. A full transcriptome microarray analysis was performed using the human Clariom™ S Assay platform (Affymetrix, 3450 Central Expy, Santa Clara, CA, 95051, USA). A comparison of the expression profiles of patients with breast cancer before and after NAC, depending on the status of hematogenous metastasis, was conducted. It was shown that the amount of DEGs in the tumor was reduced by more than six times after NAC. The top 10 signaling pathways were also found, the activity of which varied depending on the status of hematogenous metastasis before and after NAC. In addition, the association of DEGs with hematogenous metastasis in patients with breast cancer was evaluated: MFS was assessed depending on the expression level of 21 genes. It was shown that MFS was significantly associated with the expression level and pattern of nine genes. The expression levels of nine DEGs in the tumors of patients with breast cancer after NAC were significantly correlated with MFS when the status of hematogenous metastasis was taken into account.
NAC 期间分子遗传特征变化的评估以及残留肿瘤中分子特征之间的关系，是识别乳腺癌治疗结果的有效标志物的有前途的方法。文献中的大多数数据都展示了分子遗传特征与 NAC 反应之间的关系，或者只是描述性的。本研究旨在确定 NAC 期间表达谱的变化，并根据远处血行转移评估 luminal B HER2 型乳腺癌患者的基因表达与预后之间的关系。本研究纳入了 39 例 luminal B HER2-BC 患者。患者接受了 6-8 个疗程的 NAC，分析了包含活检和手术标本的配对样本。使用人类 Clariom ™ S 检测平台（Affymetrix，3450 Central Expy，Santa Clara，CA，95051，USA）进行了全转录组微阵列分析。比较了 NAC 前后乳腺癌患者的表达谱，根据血行转移的状态进行了比较。结果表明，NAC 后肿瘤中 DEGs 的数量减少了六倍以上。还发现了前 10 个信号通路，它们的活性在前 NAC 和后 NAC 时根据血行转移的状态而有所不同。此外，还评估了 DEGs 与乳腺癌患者血行转移的相关性：MFS 取决于 21 个基因的表达水平。结果表明，MFS 与 9 个基因的表达水平和模式显著相关。考虑到血行转移的状态，NAC 后乳腺癌患者肿瘤中 9 个 DEGs 的表达水平与 MFS 显著相关。
