Prognostic value of TMPRSS4 expression in patients with breast cancer

Transmembrane protease, serine 4 (TMPRSS4), is a novel type II transmembrane serine protease that is highly expressed on the cell surface in pancreatic, thyroid, lung, and other cancer tissues, although its oncogenic significance and molecular mechanisms are unknown. In a series of 109 primary breast cancer patients, we performed a comprehensive analysis of TMPRSS4 expression using immunohistochemistry. The relationship between TMPRSS4 expression and the clinicopathological characteristics or prognosis was evaluated. Results showed that breast cancer tissues exhibited higher levels of TMPRSS4 expression compared with benign tissues (65.1 versus 17.5 %, P < 0.001). High expression of TMPRSS4 was significantly correlated with lymph node metastasis (P < 0.001), high pathological grade (P = 0.001), and tumor size >2 cm (P = 0.006), but not correlated with other clinicopathological parameters, including the patient's age (P = 0.289), menopausal status (P = 0.300), histological subtype (P = 0.418), and status of estrogen receptor (ER) (P = 0.913), progesterone receptor (PR) (P = 0.247), and HER-2 (P = 0.882). Patients with high expression of TMPRSS4 had shorter OS and DFS than those with low expression (P = 0.0009 and P = 0.0044, respectively). TMPRSS4 expression and lymph node metastasis were independent prognostic factors for both OS and DFS by multivariate analysis. Based on our results, we propose TMPRSS4 as a putative biological marker for breast cancer and as an indicator of poor prognosis.