NDC80 Enhances Cisplatin-resistance in Triple-negative Breast Cancer

Abstract

Backgrounds: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Chemotherapy; Cisplatin; NDC80; Resistance; Triple-negative breast cancer.