BackgroundMost patients with breast cancer in advanced stages of the disease suffer from bone metastases which lead to fractures and nerve compression syndromes. microRNA dysregulation is an important event in the metastases of breast cancer to bone. microRNA-124 (miR-124) has been proved to inhibit cancer progression, whereas its effect on bone metastases of breast cancer has not been reported. Therefore, this study aimed to investigate the role and underlying mechanism of miR-124 in bone metastases of breast cancer.MethodsIn situ hybridization (ISH) was used to detect the expression of miR-124 in breast cancer tissues and bone metastatic tissues. Ventricle injection model was constructed to explore the effect of miR-124 on bone metastasis in vivo. The function of cancer cell derived miR-124 in the differentiation of osteoclast progenitor cells was verified in vitro. Dual-luciferase reporter assay was conducted to confirm Interleukin-11 (IL-11) as a miR-124 target. The involvement of miR-124/IL-11 in the prognosis of breast cancer patients with bone metastasis was determined by Kaplan-Meier analysis.ResultsHerein, we found that miR-124 was significantly reduced in metastatic bone tissues from breast cancers. Down-regulation of miR-124 was associated with aggressive clinical characteristics and shorter bone metastasis-free survival and overall survival. Restoration of miR-124 suppressed, while inhibition of miR-124 promoted the bone metastasis of breast cancer cells in vivo. At the cellular level, gain of function and loss-of function assays indicated that cancer cell-derived miR-124 inhibited the survival and differentiation of osteoclast progenitor cells. At the molecular level, we demonstrated that IL-11 partially mediated osteoclastogenesis suppression by miR-124 using in vitro and in vivo assays. Furthermore, IL-11 levels were inversely correlated with miR-124, and up-regulation IL-11 in bone metastases was associated with a poor prognosis.ConclusionsThus, the identification of a dysregulated miR-124/IL-11 axis helps elucidate mechanisms of breast cancer metastases to bone, uncovers new prognostic markers, and facilitates the development of novel therapeutic targets to treat and even prevent bone metastases of breast cancer.Electronic supplementary materialThe online version of this article (10.1186/s12943-017-0746-0) contains supplementary material, which is available to authorized users.

PurposeOur study aimed to describe the clinical features of undifferentiated pleomorphic sarcoma (UPS) and identify the predictors of poor outcomes.Patients and methodsThe clinicopathological variables and treatment strategies of 100 UPS patients who underwent surgical resections at a single institution between November 2004 and July 2016 were reviewed. Kaplan–Meier and Cox regression method were conducted for survival analysis.ResultsThe median follow-up time was 94 months (range, 1.5–154 months). R0 resection was applied for 72 cases, and the median tumor size was 5.75cm (range, 1–30cm). Tumor grades of 45 patients were intermediate grade (G2), and 54 patients were with advanced stage (stage III/IV). Twenty-seven patients presented with tumors involving important structures, in which the nerve was the most frequently invaded structure (n=12). During the follow-up, 40 patients suffered from postoperative local recurrence, and distant metastasis was observed in 25 patients which mainly metastasized to the lung (n=14). The 5-year OS rate, 5-year LRFS rate, and 5-year MFS rate was 53%, 55%, and 70%, respectively. Multivariate analysis revealed that tumor presentation, tumor size, and important structures involved (p=0.033, p=0.004, and p=0.033, respectively) were independent prognostic factors associated with OS. Meanwhile, age, resection quality and tumor grade were independent prognostic factors for LRFS (p=0.033, p=0.045, and p=0.007, respectively) and tumor depth was significantly associated with MFS (p=0.050) in multivariate analysis.ConclusionPrimary treatment of UPS should be conducted by experts in large sarcoma center. Wide surgical margin provides sufficient control of the disease recurrence.

Background: To describe the clinical features of retroperitoneal dedifferentiated liposarcoma (RP DDLS) and further evaluate the prognostic factors.Methods: The clinicopathological variables and treatment strategies of 61 RP DDLS patients who underwent surgical resections at a single institution between September 2005 and September 2016 were reviewed. Kaplan-Meier and Cox regression methods were conducted for survival analyses.Results: The average patients' age was 52 years (range, 27-81), and there was almost no gender predilection (30 males vs. 31 females). 51 (83.6%) patients got gross tumor resections (R0/R1 resection), and the median tumor size was 19 cm (range, 4.3-50 cm). 39(63.9%) patients were with intermediate-grade sarcoma and 22(36.1%) were with high-grade sarcoma. The median intraoperative blood loss was 400 ml (range, 50-2700ml). 19 (31.1%) patients presented multifocal diseases. Tumors were removed intactly in 42 (68.9%) patients. In order to obtain gross tumor resections, 33 (54.1%) of the patients underwent excisions of at least one adjacent organ, of which kidney (n=21, 63.6%) was the most common one. 6 (9.8%) patients developed distant metastases during follow-up. The overall 5-year progression-free survival (PFS) rate was 3.7%, with the median PFS of 19 months. The 5-year overall survival (OS) rate was 43.5%, with the median OS of 58 months. Updating to November 2017, 30 (49.2%) patients remained alive. The median follow-up time was 49 months. Multivariate analysis using Cox proportional hazards model revealed that tumor grade, blood loss, resection extent, and tumor integrity were independently associated with OS (p=0.032, p=0.018, p=0.020, p=0.005, respectively). Tumor grade, tumor integrity and multifocality were significant predictors for PFS (p=0.013, p=0.080, p=0.009, p=0.028, respectively).Conclusion: Intermediate-grade histology, intraoperative blood loss < 400 ml, complete tumor resection, and tumor integrity were independently associated with better OS. Intermediate-grade histology, tumor integrity and unifocal disease independently predicted favorable PFS.

No abstract