Abstract
The sex-determining region Y-box 12 (SOX12) is implicated in several oncogenic signaling pathways of multiple types of cancer; however, the biological effects of SOX12 on breast cancer has yet to be elucidated. Here, we assessed SOX12 expression using real-time quantitative PCR in 142 pairs of breast cancer and adjacent normal tissues (ANTs) and immunohistochemistry in 524 breast cancer and 147 ANTs. The effects of SOX12 on breast cancer progression, clinicopathological variables, and prognostic value were then investigated. SOX12 expression was markedly elevated in breast cancer tissues relative to that in ANTs at both mRNA and protein levels. Positive SOX12 expression was correlated to tumor size (P = 0.005), estrogen receptor (ER) (P = 0.018) and human epidermal growth factor receptor (HER2) (P = 0.004) status, lymph node metastasis (P < 0.001), and the tumor-node-metastasis (TNM) stage (P < 0.001). Notably, the positive rate of SOX12 expression gradually increased with breast cancer progression. Multivariate analysis indicated that SOX12 was an independent prognostic factor for overall survival (OS, P = 0.023) and distant metastasis-free survival (DMFS, P = 0.012). Subgroup analysis revealed that luminal and HER2 patients with positive SOX12 expression had a shorter OS period than those with negative SOX12 expression. Moreover, SOX12 expression was associated with a high risk of distant metastasis in invasive carcinoma with the lymph node metastasis subgroup. In summary, SOX12 correlates with progression and poor prognosis in human breast cancer, suggesting that SOX12 is a potential target for breast cancer treatment and warrants further functional research.