WNT1 inducible signaling pathway protein 1 (WISP1) plays a key role in many cellular functions in a highly tissue-specific manner; however the role of WISP1 in breast cancer is still poorly understood. Here, we demonstrate that WISP1 acts as an oncogene in human breast cancer. We demonstrated that human breast cancer tissues had higher WISP1 mRNA expression than normal breast tissues and that treatment of recombinant WISP1 enhanced breast cancer cell proliferation. Further, ectopic expression of WISP1 increased the growth of breast cancer cells in vitro and in vivo. WISP1 transfection also induced epithelial-mesenchymal-transition (EMT) in MCF-7 cells, leading to higher migration and invasion. During this EMT-inducing process, E-cadherin was repressed and N-cadherin, snail, and β-catenin were upregulated. Filamentous actin (F-actin) remodeling and polarization were also observed after WISP1 transfection into MCF-7 cells. Moreover, forced overexpression of WISP1 blocked the expression of NDRG1, a breast cancer tumor suppressor gene. Our study provides novel evidence that WISP1-modulated NDRG1 gene expression is dependent on a DNA fragment (−128 to +46) located within the human NDRG1 promoter. Thus, we concluded that WISP1 is a human breast cancer oncogene and is a potential therapeutic target.
This study aimed to investigate the prognostic value of the preoperative neutrophil to lymphocyte ratio (NLR) in resectable gastric cancer (GC).This was a retrospective review of 1030 patients with resectable GC managed between 2005 and 2011. Patients were stratified into 2 groups, those with a preoperative NLR >3.44 and those with a preoperative NLR ≤3.44. Clinicopathological data affecting patient prognosis were collected prospectively and analyzed.The high NLR (>3.44) group had a higher proportion of a platelet to lymphocyte ratio >132, tumor size >4.8 cm, T4 lesions, metastatic tumors, a ratio of metastatic to examined lymph nodes >0.18, positive resection margins, and presence of vascular or lymphatic invasion than the low NLR (≤3.44) group. Patients with a high preoperative NLR had significantly lower 3- and 5-year overall survival rates than those with a low preoperative NLR (55.1% vs 71.0% and 47.2% vs 64.1%, respectively; P < 0.001). Preoperative NLR was a prognostic factor for resectable GC in multivariate analysis.More aggressive tumor behavior was observed in patients with resectable GC with a high preoperative NLR than in those with a low preoperative NLR. High preoperative NLR was an independent unfavorable prognostic factor. Measurement of this ratio may serve as a clinically accessible and useful biomarker for patient outcomes.
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