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...

There is sufficient evidence that human stomatin-like protein 2 (SLP-2) is a novel cancer-related gene. Its protein is overexpressed in many human cancers. SLP-2 can contribute to the promotion of cell growth, cell adhesion, and tumorigenesis in esophageal squamous cell carcinoma and lymph node metastasis in laryngeal squamous cell carcinoma. Immunohistochemical detection of SLP-2, estrogen and progesterone receptors, and HER-2/neu were performed on 263 cases of primary invasive breast cancer with a tissue microarray. Of 263 cases, 138 (52.5%) showed high expression of SLP-2 protein, and 125 (47.5%) showed low or absent expression. In addition, there were significant positive associations between tumor stage and size (P = .020), lymph node metastasis (P < .001), clinical stage (P < .001), distant metastasis (P = .002), and HER-2/neu protein expression (P = .037) and high-level SLP-2 expression. High-level SLP-2 expression was associated with decreased overall survival (P = .011) and was more often found in patients with tumors larger than 20 mm, lymph node metastasis, advanced clinical stage, distant metastasis, and HER-2/neu protein-positive expression. More important, lymph node metastasis, HER-2/neu-positive expression, and high-level SLP-2 expression were associated with significantly decreased survival.

Breast cancer is the most common malignant tumor and the main cause of cancer-associated mortality in females worldwide. Long non-coding RNAs (lncRNAs) have been reported to play vital roles in breast cancer development and progression; however, our understanding of most lncRNAs in breast cancer is still limited. In this study, we demonstrated that small nucleolar RNA host gene 5 (SNHG5) promotes breast cancer cell proliferation both in vitro and in vivo , and depletion of SNHG5 significantly led to cell-cycle arrest at G1 phase. Accumulating evidence has shown that many lncRNA transcripts could function as competing endogenous RNAs (ceRNAs) by competitively binding common microRNAs (miRNAs). We found that SNHG5 acts as a sponge for miR-154-5p, reducing its ability to repress proliferating cell nuclear antigen (PCNA). SNHG5 promoted breast cancer proliferation and cell-cycle progression by upregulation of PCNA expression. Clinically, we observed an increased SNHG5 expression in breast cancer, whereas miR-154-5p was decreased in breast cancer tissues compared with the adjacent normal breast tissues. Furthermore, the SNHG5 expression was significantly negatively correlated with miR-154-5p expression. Taken together, our data uncover the SNHG5-miR-154-5p-PCNA axis and provide a novel mechanism to explain breast cancer proliferation.

Glycogen-rich clear cell carcinoma (GRCC) of the breast is a rare type of breast carcinoma. Knowledge about the characteristics of this type is fragmentary, and the prognosis is on debate. In this study, we aimed to summarize the clinical, pathologic, and biologic characteristics of GRCC of the breast and analyze the survival. We reviewed the cases of breast cancer in our hospital between January 1999 and December 2009 and identified 28 patients as GRCC of the breast. The routine hematoxylin-eosin staining, periodic acid-Schiff (PAS) staining, and diastase PAS staining were performed on the tumor tissues. The expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), Ki67 and P53 were evaluated by immunohistochemistry. Tumors with a HER-2 score of 2+ were confirmed by fluorescent in situ hybridization test. Each GRCC case, who had complete follow-up data, was compared with four cases of usual invasive ductal carcinomas as controls in the same database and matched with age, year of diagnosis, tumor size, nodal status, and immunophenotype. The chi-squared test and the Fisher's exact test were used to compare the characteristics of GRCC cases and controls. The univariate analysis was used to study the prognosis, and Kaplan-Meier method was used to compare the survival of two groups. The clinicopathologic and imaging features were analyzed in the GRCC cases. Tumor sizes ranged from 0.8 to 7.5 cm (mean, 3.2 cm). Thirteen cases (46.4%) had positive lymph nodes. The positivity of ER and PR was 61.5% (16 of 26). HER-2 was positive for three cases (12%). The positivity of Ki67 and P53 were 87.5% and 45.8%, respectively. Twenty-four cases were followed up from 19 to 158 months. The prognosis of GRCC of the breast was significantly related with the number of positive lymph nodes (p < 0.001), and patients with more than 10 positive lymph nodes were at high risk of recurrence or metastasis. There was no significant difference in overall survival (p = 0.547), and disease-free survival (p = 0.900) between GRCC of the breast and the usual invasive ductal carcinomas. GRCC of the breast may not have a worse survival.

The purpose of this study was to investigate whether pre-operative prognostic nutritional index (PNI), an indicator of nutritional and immunological status, has an impact on the long-term outcomes in triple-negative breast cancer (TNBC) patients. This retrospective study reviewed the medical records of 382 TNBC patients who had suffered from mastectomy. Pre-operative PNI was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count (per mm(3)). The receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff value of PNI. The correlations of PNI value with clinicopathological features were analyzed and the univariate and multivariate analysis were applied to identify the prognostic factors. The results showed that pre-operative PNI value was significantly related to advanced tumor status such as N stage (p = 0.011), T stage (p = 0.015), and recurrence incidents (p = 0.001). Survival analysis identified PNI as an independent prognostic factor for TNBC. Patients with higher PNI value had better 5-year disease-free survival (DFS) and 5-year overall survival (OS) than those with lower PNI value (DFS, p = 0.007; OS, p = 0.011). Taken together, our results suggest that the pre-operative PNI can be used as a simple and useful marker for predicting the long-term outcomes of TNBC patients.