A Promising Predictor of the Efficacy of Endocrine Therapy for Breast Cancer:14-3-3-zeta

Shunchao Yan; Xin Jiao; Na Li; Yangfan Du

摘要：Objective 14-3-3-zeta protein has been found to be associated with survival signaling in cancer. However, prognos-tic value and the predictive effect of its gene expression for determining the efficacy of endocrine therapy in breast cancer are unclear. Methods The differential 14-3-3-zeta gene expression between cancer and normal tissue was assayed using ONCOMINE database analysis. The correlation between 14-3-3-zeta gene and proliferative/metastasis-associated genes was analyzed using Breast Cancer Gene-Expression Miner v4. 1 (bc-GenExMiner v4. 1). The prognostic value of its ex-pression in breast cancer was analyzed using bc-GenExMiner v4. 1 and Kaplan-Meier Plotter. Results The 14-3-3-zeta gene expression was elevated in breast cancer tissue compared with normal breast tissue,which was higher in invasive ductal breast cancer than in ductal breast cancer in situ. It was also positively correlated with the degree of malignancy and the clinical stage of breast cancer and with some proliferative genes. A high level of 14-3-3-zeta expression was predictive of shorter relapse-free survival ( RFS) in ER-positive but not ER-negative breast cancer. Further analysis showed the associ-ation of high 14-3-3-zeta expression and a shorter RFS in endocrine therapy or tamoxifen-only-treated population, re-gardless of whether chemotherapy had been used. Conclusion 14-3-3-zeta gene expression is upregulated and associated with a relatively high degree of malignancy and late clinical stage in breast cancer. It is a promising prognostic factor for ER-positive breast cancer and a predictor of the efficacy of endocrine therapy.