Background: Experimental evidence suggests that matrix metalloproteinase-13 (MMP-13) protein may promote breast tumor progression. However, its relevance to the progression of human breast cancer is yet to be established. Furthermore, it is not clear whether MMP-13 can be used as an independent breast cancer biomarker. This study was conducted to assess the expression profile of MMP-13 protein in invasive breast carcinomas to determine its diagnostic and prognostic significance, as well as its correlation with other biomarkers including estrogen receptor (ER), progesterone receptor (PR), Her-2/neu, MMP-2, MMP-9, tissue inhibitor of MMP-1 and -2 (TIMP-1 and TIMP-2).

BackgroundBreast cancer is the most common cancer among women worldwide and metastasis is the leading cause of death among patients with breast cancer. The transforming growth factor-β (TGF-β) pathway plays critical roles during breast cancer epithelial–mesenchymal transition (EMT) and metastasis. SMAD2, a positive regulator of TGF-β signaling, promotes breast cancer metastasis through induction of EMT.MethodsThe expression of miR-190 and SMAD2 in breast cancer tissues, adjacent normal breast tissues and cell lines were determined by RT-qPCR. The protein expression levels and localization were analyzed by western blotting and immunofluorescence. ChIP and dual-luciferase report assays were used to validate the regulation of ZEB1-miR-190-SMAD2 axis. The effect of miR-190 on breast cancer progression was investigated both in vitro and in vivo.ResultsmiR-190 down-regulation is required for TGF-β-induced EMT. miR-190 suppresses breast cancer metastasis both in vitro and in vivo by targeting SMAD2. miR-190 expression is down-regulated and inversely correlates with SMAD2 in breast cancer samples, and its expression level was associated with outcome in patients with breast cancer. Furthermore, miR-190 is transcriptionally regulated by ZEB1.ConclusionsOur data uncover the ZEB1-miR-190-SMAD2 axis and provide a mechanism to explain the TGF-β network in breast cancer metastasis.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0818-9) contains supplementary material, which is available to authorized users.

Neutropenia is one of the most important dose-limiting toxicities and often the reason for dose reduction. In this study we aimed to assess whether chemotherapy-induced neutropenia could be a marker of efficacy and associate with increased survival. Data from a retrospective survey for early breast cancer patients in our hospital were reviewed. Three hundred and thirty-five patients who had been treated with six cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF) were studied. The association between chemotherapy-induced neutropenia and overall survival (OS) was assessed. According to a multivariate Cox model with time-varying covariates, hazard ratios of death were 0.434 (95% confidence interval (CI), 0.298-0.634; P < 0.001) for patients with mild neutropenia, and 0.640 (95% CI, 0.42-0.975; P = 0.038) for those with severe neutropenia. Neutropenia occurring in early breast cancer patients is an independent predictor of increased survival. These findings suggest that neutropenia in patients who receive chemotherapy is strongly associated with a better prognosis.

The role of insulin-like growth factor binding protein 5 (IGFBP5) in tumorigenesis and development of cancer is not well-defined. IGFBP5 has been shown to either stimulate or inhibit cell proliferation via an IGF-dependent mechanism and to promote cell proliferation and migration in an IGF-independent manner. In the authors' previous study, IGFBP5 was found to be significantly up-regulated in lymph node metastases compared with their paired primary breast cancers. To further determine the role of IGFBP5 in breast cancer development and to evaluate its clinical significance in breast cancer, the mRNA expression level was detected in 30 normal breast tissues, 108 primary tumors, and 30 lymph node metastases using real time reverse transcription-polymerase chain reaction. The expression levels were correlated with several clinical parameters, including clinical stage, pathologic tumor size, axillary lymph node status, nuclear grade, estrogen receptor status, Her2 status, and local relapse or distant metastasis of the patients. As a result, the expression of IGFBP5 mRNA correlated positively with the invasion of axillary lymph nodes and the status of hormonal receptor. T he insulin-like growth factor binding protein 5 (IGFBP5) belongs to a protein family of at least six members that binds to insulin-like growth factor (IGF). In humans, the IGFBP5 gene spans 33 kb and is located on 2q33-q36. The mature IGFBP5 protein consists of 252 amino acids and has a molecular mass of approximately 29 kDa. IGFBP5 was initially recognized as a secreted protein that binds to IGF with high affinity by its N-terminal motif and modulates their mitogenic and anti-apoptotic effects by either inhibiting or augmenting the interaction of IGF with their cell-surface receptor (IGF-IR). IGFBP5 has been shown to inhibit the proliferative responses of skeletal muscle cells (1) and breast cancer cells (2) to IGF-I. In contrast, in bone, (3) fibroblast, (4) osteoblasts, (5) and vascular smooth muscle cells, (6) IGFBP5 has been found to potentiate the effect of IGF on cell growth. The complexity of the cellular function of IGFBP and its regulation is further revealed by recent studies that have shown that IGFBP5 also stimulates cell growth, (7,8) migration, (6,9,10) and cell attachment to extracellular matrix (ECM) (11,12) through IGF-independent mechanisms. Thus, the role of IGFBP5 in cancer is far from being clear.In the authors' previous study of breast cancer tissues,it was found that IGFBP5 was significantly up-regulated in lymph node metastases relative to their paired primary cancers, suggesting that IGFBP5 may play an important role in the metastasis of breast cancer. Additional studies have supported the notion that IGFBP5 overexpression contributes to metastasis and poor prognosis of cancer. Wang et al. have demonstrated a strong correlation between overexpression of IGFBP5 and the histologic grade of ovarian cancer and glioblastoma. (14,15) And up-regulated IGFBP5 was included in the 'poor prognosis signature' in a study by van't Veer e...