Abstract
SIRT1 expression and Notch1 signaling have been implicated in tumorigenesis in many cancers, but their association with survival in breast cancer has not been determined. The purpose of this study was to assess the possible prognostic value of SIRT1, N1IC, and Snail expression in breast cancer patients. Immunohistochemistry was performed to examine the expression of SIRT1, N1IC, and Snail, and the combined expression of SIRT1 and N1IC, using tissue microarrays containing breast cancer tissue and matched adjacent normal breast tissue from 150 breast cancer patients. Survival analysis was carried out using the Kaplan-Meier method. Univariate and multivariate analysis were used to evaluate the prognostic value of SIRT1, N1IC, Snail and combined SIRT1/N1IC expression, in addition to other clinicopathological factors, including grade, lymph node status, disease stage, and estrogen, progesterone, and human epidermal growth factor receptor 2 receptor status in breast carcinoma patients. SIRT1, N1IC, and Snail were all found to be highly expressed and an inverse correlation between SIRT1 and N1IC in breast cancer tissue. The three markers significantly correlated with lymph node status. Patients with low SIRT1 expression exhibited shorter overall survival (OS) and disease-free survival (DFS), and patients with combined low expression of SIRT1 and high expression of N1IC had the worse OS and DFS. Univariate and multivariate survival analysis revealed that low expression of SIRT1 and SIRT1-low/N1IC-high expression were independent prognostic factors for poor survival. These results suggest that low expression of SIRT1 or the combined low expression of SIRT1 and high expression of N1IC could be used as indicators of poor prognosis, and may represent novel therapeutic targets in breast cancer.
Highlights
Breast cancer is one of the leading causes of cancer mortality in women worldwide
SIRT1 and Snail were predominantly localized in the nucleus, while Notch1 intracellular domain (N1IC) staining was located in the nucleus and/or cytoplasm
The results showed the expression level of SIRT1 protein was significantly lower in cancer than normal tissues (p = 0.000), the expression level of N1IC and Snail were markedly up-regulated in cancer tissues (p = 0.027, p = 0.001, respectively)
Summary
Breast cancer is one of the leading causes of cancer mortality in women worldwide. Certain clinicopathological factors such as histological grade, lymph node metastasis, tumor-node-metastasis (TNM) stage, and hormonal status have been widely used to predict clinical outcome. Some studies have found that SIRT1 expression is significantly associated with poor survival [8,9,10], while, in contrast, others reported an association with good prognosis in breast carcinoma [5,11,12]. The purpose of this study was to assess the possible prognostic value of SIRT1, N1IC, and Snail expression in breast cancer patients
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