Abstract
Triple-negative breast cancer (TNBC) is characterized by the lack of immunohistochemical staining for estrogen receptors (ER), progesterone receptors (PR), and lack of overexpression or amplification of human epidermal growth factor receptor 2 (HER2). Our aim was to investigate the expression of transmembrane protease, serine 4 (TMPRSS4) in TNBC patients and its possible relationship to the outcome of the disease. A total of 72 TNBC patients and 109 non-TNBC patients who were diagnosed between 2003 and 2008 were enrolled in this study. Immunohistochemistry was used to compare the expression pattern of TMPRSS4 in TNBC and non-TNBC groups, and the prognostic significance was assessed by Kaplan-Meier analysis and Cox proportional hazards regression in TNBC patients. The rate of high expression of TMPRSS4 was significantly higher in TNBC group than that in non-TNBC group. High expression of TMPRSS4 was significantly correlated with lymph node metastasis, histological grade, and tumor size. TNBC patients with high TMPRSS4 expression showed the poorer overall survival (OS) and disease-free survival (DFS) than those patients with low TMPRSS4 expression. In multivariate analysis, only lymph node metastasis and TMPRSS4 expression were the independent prognostic factors for OS and DFS in TNBC. Our study provides evidence that TMPRSS4 expression is associated with lymph node metastasis, tumor size, and histological grade in TNBC patients, and also is an independent prognostic factor for TNBC.
Highlights
Breast cancer remains the most frequently diagnosed female cancer worldwide and the leading cause of cancer death, despite screening and improvements in adjuvant treatment [1]
The rate of high expression of TMPRSS4 was significantly higher in Triple-negative breast cancer (TNBC) group (73.6%) than that in non-TNBC group (55.0%) (p = 0.012)
Comparison of clinical features between TNBC group and non-TNBC group showed that histological subtype (p = 0.003), lymph node metastasis (p = 0.004) and tumor size (p = 0.048) were significantly different
Summary
Breast cancer remains the most frequently diagnosed female cancer worldwide and the leading cause of cancer death, despite screening and improvements in adjuvant treatment [1]. Due to high rates of visceral and central nervous system metastases, patients with TNBC have a poorer disease specific survival than hormone receptor-positive subtypes [5,6,7]. Predictive and prognostic factors of TNBC phenotype are poorly understood. There is an urgent need to identify new prognostic biomarkers that can be used to predict a therapeutic response and clinical outcomes in TNBC patients to rationalize treatment decisions. Transmembrane protease, serine 4 (TMPRSS4), as a member of TTSPs, was first discovered by differential gene analysis for pancreatic cancer markers [11]. Several studies have reported high expression at the transcriptional level in colorectal, thyroid, lung, and pancreatic cancer by Northern blot analyses, microarray gene chips, and RT-PCR. Further analysis of TMPRSS4-mediated signaling in colon cancer cells suggested that multiple downstream signaling pathways are activated including focal adhesion kinase (FAK) and extracellular signal regulated kinase (ERK) resulting in the downregulation of
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