Sineoculis homeobox homolog 1 protein is associated with breast cancer progression and survival outcome

Abstract

Sineoculis homeobox homolog 1 (SIX1) is one of the transcription factors that act as master regulators of development and is frequently dysregulated in cancer. This study explores the roles of SIX1 in tumor progression and as a prognostic determinant of breast cancer. Breast cancer specimens from 262 patients were selected for analysis of SIX1 protein by immunohistochemistry (IHC). The localization of SIX1 protein was detected in MDA-MB468 breast cancer cells using immunofluorescence (IF) staining. The survival rates were calculated by the Kaplan–Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models. SIX1 protein mainly showed cytoplasmic/perinuclear staining pattern in breast cancer using IHC in paraffin embedded breast cancer tissues and IF in MDA-MB468 cancer cells. The strongly positive rate of SIX1 protein was 61.8% (162/262) in breast cancer and 23.1% (12/52) in ductal carcinoma in situ (DCIS), which was significantly higher than adjacent normal breast tissues (6.7%, 3/45). SIX1 overexpression was positively correlated with clinical stage, lymph node metastasis, Her2 expression status, and disease-free survival (DFS) and 5-year overall survival (OS) rates of patients with breast cancer. Moreover, patients with late stage breast cancer and high SIX1 expression had poorer survival rates than those with low SIX1 expression. Further analysis using a Cox proportional hazard regression model revealed that high SIX1 expression emerged as a significant independent hazard factor for the DFS and OS rates of patients with breast cancers along with Her2 status and clinical stage. SIX1 may potentially be used as an independent biomarker for prognostic evaluation of breast cancer.