Li Jing, Xu Xiaoqin, Peng Xiting
Department of Thyroid and Breast Surgery, The First People's Hospital of Jingmen, Jingmen, Hubei, China.
Department of Radiology, Taizhou Municipal Hospital, Taizhou, Zhejiang, China.
Arch Med Res. 2022 Jun;53(4):378-387. doi: 10.1016/j.arcmed.2022.03.003. Epub 2022 Mar 26.
Chemotherapy is a standard systemic treatment option for triple-negative breast cancer (TNBC). Cisplatin has been used to treat TNBC, but frequently leads to cisplatin resistance in patients. The aim of our study was to investigate cisplatin-resistant mechanism in TNBC.
To identify the potential genes and pathways relative to cisplatin resistance, GSE103115 data were analyzed by the Limma package and Gene set enrichment analysis (GSEA). TNBC data from TCGA, GSE76250 and GSE115275 datasets were used to calculate NDC80 expression. Immunohistochemistry detected NDC80 protein expression in TNBC tissues from patients before and after cisplatin treatment. After expose to cisplatin treatment, the viability and proliferation of TNBC cells were measured by CCK-8 and colony formation assays, respectively.
NDC80 was regarded as a cisplatin-resistant gene because after cisplatin treatment NDC80 was downregulated in cisplatin-sensitive cells but was upregulated in cisplatin-resistant cells. NDC80 was over-expressed in TNBC tissues compared to normal tissues. Furthermore, NDC80 expression in TNBC patients was increased after cisplatin treatment. Cisplatin-sensitive TNBC patients showed lower NDC80 expression than cisplatin-resistant patients. Additionally, NDC80 expression was correlated with clinical stages, tumor size and chemotherapy of TNBC patients. Moreover, NDC80 overexpression promoted the viability and proliferation of TNBC cells and enhanced the cells resistance to cisplatin. The potential pathways relative to cisplatin resistance were obtained, such as p53 signaling pathway and Oxidative phosphorylation.
These findings provide new insights for understanding the mechanism of cisplatin resistance in TNBC, and NDC80 may be a potential therapeutic target for TNBC treatment.
化疗是三阴性乳腺癌（TNBC）的标准全身治疗选择。顺铂已被用于治疗TNBC，但患者常出现顺铂耐药。本研究旨在探讨TNBC中的顺铂耐药机制。
为鉴定与顺铂耐药相关的潜在基因和通路，利用Limma软件包和基因集富集分析（GSEA）对GSE103115数据进行分析。使用来自TCGA、GSE76250和GSE115275数据集的TNBC数据计算NDC80表达。免疫组化检测顺铂治疗前后患者TNBC组织中NDC80蛋白表达。顺铂处理后，分别通过CCK-8和集落形成试验检测TNBC细胞的活力和增殖。
NDC80被视为顺铂耐药基因，因为顺铂处理后，NDC80在顺铂敏感细胞中下调，但在顺铂耐药细胞中上调。与正常组织相比，NDC80在TNBC组织中过表达。此外，顺铂治疗后TNBC患者的NDC80表达增加。顺铂敏感的TNBC患者NDC80表达低于顺铂耐药患者。此外，NDC80表达与TNBC患者的临床分期、肿瘤大小和化疗相关。而且，NDC80过表达促进TNBC细胞的活力和增殖，并增强细胞对顺铂的耐药性。获得了与顺铂耐药相关的潜在通路，如p53信号通路和氧化磷酸化。
这些发现为理解TNBC中顺铂耐药机制提供了新见解，NDC80可能是TNBC治疗的潜在靶点。
