Decreased Nek9 expression correlates with aggressive behaviour and predicts unfavourable prognosis in breast cancer

As a new member of Neks family, Nek9 regulates spindle assembly and controls chromosome alignment and centrosome separation. In the current study we aimed to investigate the expression of Nek9 in breast cancer and its clinical significance. We evaluated the expression of Nek9 in invasive ductal carcinoma (IDC, n=316), ductal carcinoma in situ (DCIS), usual ductal hyperplasia, atypical ductal hyperplasia, fibroadenoma and normal breast tissues using immunohistochemistry. The results revealed significantly reduced Nek9 in IDCs (41.8%) compared to benign breast lesions. Moreover, gradually reduced Nek9 was found from DCIS to invasive carcinoma and metastatic tumour within the same tumours. The decrease in Nek9 expression was associated with larger tumour size (p=0.0087), high grade (p<0.0001) and high Ki-67 index (p<0.0020). TCGA and GEO datasets analysis revealed low level of Nek9 mRNA was more frequent in triple negative breast cancers, and associated with poor overall survival and distant metastasis-free survival. These findings suggest an important role of Nek9 in the progression of breast cancer, and aberrantly expressed Nek9 correlates with more aggressive clinicopathological variables and predicts poor clinical prognosis. Nek9 may serve as a potential predictive factor for patients with breast cancer.