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Purpose: We aimed to construct universally applicable nomograms incorporating prognostic factors to predict the prognosis of patients with triple-negative breast cancer (TNBC). Patients and methods: Clinicopathological data of 379 patients with TNBC from March 2008 to June 2014 were retrospectively collected and analyzed. The endpoints were disease-free survival (DFS) and overall survival (OS). Patients were randomly divided into a training group and an independent validation group. In the training group, the prognostic factors were screened to develop nomograms. C-index and calibration curves were used to evaluate the predictive accuracy and discriminative ability of nomograms in both groups. The accuracy of the nomograms was also compared with the traditional American Joint Committee on Cancer Tumor-Node-Metastasis anatomical stage (8th edition). Results: Four prognostic factors (albumin-to-globulin ratio, neutrophil-to-lymphocyte ratio, positive lymph nodes, and tumor size) were used to construct the nomogram of DFS. In addition to the aforementioned factors, age was taken into account in the construction of the OS nomogram. The C-index of the DFS nomogram in the training and validation groups was 0.71 (95% confidence interval [CI]: 0.64-0.77) and 0.69 (95% CI: 0.58-0.79), respectively; the C-index of the OS nomogram was 0.77 (95% CI: 0.70-0.84) and 0.74 (95% CI: 0.62-0.86), respectively. This suggests that the nomograms had high accuracy. Moreover, calibration curves showed good consistencies in both groups. Our models showed superiority in predicting accuracy compared with the AJCC TNM staging system. Furthermore, two web pages of the nomograms were produced: DFS: https://sh-skipper.shinyapps.io/TNBC1/; OS: https://sh-skipper.shinyapps.io/TNBC2/. Conclusion: These predictive models are simple and easy to use, particularly the web versions. They have certain clinical value in predicting the prognosis of patients with TNBC. They can assist doctors in identifying patients at different prognostic risks and strengthen the treatment or follow-up accordingly.

Purpose To explore the effects of the intervening measure targeting myeloid differentiation 2 (MD2) on breast cancer progression in vitro and in vivo. Methods The expression of MD2 in normal breast cells (Hs 578Bst) and three kinds of breast carcinoma cell lines (MCF-7, MDA-MB-231 s and 4T1) were detected by western blot. MTT assay was used to detect the proliferation of 4T1 cells treated by L6H21, cell migration and invasion was measured by wound healing assay and trans-well matrigel invasion assay, respectively. In addition, to further study the role of MD2 in tumor progression, we assessed the effects of inhibition of MD2 on the progression of xenograft tumors in vivo. Results The expression of MD2 is much higher in MDA-MB-231 s and 4T1cells than that in normal breast cells (Hs 578Bst) or MCF-7 cells (p < 0.05). In vitro, suppression of MD2 by L6H21 has a significant inhibition of proliferation, migration and invasion in 4T1 cells in dose-dependent manner. In vivo, L6H21 pretreatment significantly improved survival of 4T1-bearing mice (p < 0.05). Additionally, we also observed that none of the mice died from the toxic effect of 10 mg kg−1 L6H21 in 60 days. Conclusion Overall, this work indicates that suppression of MD2 shows progression inhibition in vitro and significantly prolong survival in vivo. These findings provide the potential experimental evidence for using MD2 as a therapeutic target of breast carcinoma.

Glioma is the most common type of central nervous system tumor. SWItch/sucrose non-fermentable (SWI/SNF) is a tumor suppressor that serves an important role in epithelial-mesenchymal transition (EMT). The present study aimed to identify key molecules involved in the EMT process. SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 2 (SMARCC2) is mutated in and its expression is low in multiple types of cancer. SMARCC2 is the core subunit of the chromatin-remodeling complex, SWI/SNF. Relative mRNA SMARCC2 expression levels in human glioma tissue were analyzed via reverse transcription-quantitative PCR, whereas the protein expression levels were determined via immunohistochemistry staining. SMARCC2 expression was knocked down in glioma cells using small interfering RNA (si) and overexpressed by infection with adenovirus vectors carrying SMARCC2 cDNA. Wound healing and Transwell assays were performed to assess cell migration and invasion, respectively. Subsequently, immunofluorescence and western blotting were performed to analyze the expression levels of the oncogene c-Myc, which is associated with SMARCC2. SMARCC2 combines with C-MYC to downregulate its expression. Consistent with the results of the bioinformatics analysis, which revealed that the upregulated expression levels of SMARCC2 were associated with a more favorable prognosis in patients with glioma, the mRNA and protein expression levels of SMARCC2 were significantly upregulated in low-grade glioma tissues compared with high-grade glioma tissues. The results of the wound healing assay demonstrated that cell migration was significantly increased in the siSMARCC2-1/3 groups compared with the negative control (NC) group. By contrast, the migratory ability of cells was significantly reduced following transduction with adenovirus overexpressing SMARCC2, which upregulated the expression of SMARCC2, compared with the lentiviral vector-non-specific control (LVS-NC) group. The Transwell assay results further showed that SMARCC2 overexpression significantly inhibited the migratory and invasive abilities of U87MG and LN229 cells compared with the LVS-NC group. Co-immunoprecipitation assays were subsequently conducted to validate the binding of SMARCC2 and c-Myc; the results demonstrated that the expression of c-Myc was downregulated in adenovirus-transfected cells compared with LVS-NC-transfected cells. The results of the western blotting experiments demonstrated that the expression levels of N-cadherin, vimentin, snail family transcriptional repressor 1 and β-catenin were notably downregulated, whereas the expression levels of T-cadherin were markedly upregulated in cell lines stably overexpressing SMARCC2 compared with the LVS-NC group. In conclusion, the results of the present study suggested that SMARCC2 may inhibit Wnt/β-catenin signaling by regulating c-Myc expression in glioma. SMARCC2 regulates the EMT status of the glioblastoma cell line by mediating the expression of the oncogene C-MYC to inhibit its migration and ...