Predictive nomogram based on serum tumor markers and clinicopathological features for stratifying lymph node metastasis in breast cancer.

BACKGROUND: This study was aimed to establish the nomogram to predict patients' axillary node status by using patients' clinicopathological and tumor characteristic factors. METHODS: A total of 705 patients with breast cancer were enrolled in this study. All patients were randomly divided into a training group and a validation group. Univariate and multivariate ordered logistic regression were used to determine the predictive ability of each variable. A nomogram was performed based on the factors selected from logistic regression results. Receiver operating characteristic curve (ROC) analysis, calibration plots and decision curve analysis (DCA) were used to evaluate the discriminative ability and accuracy of the models. RESULTS: Logistic regression analysis demonstrated that CEA, CA125, CA153, tumor size, vascular-invasion, calcification, and tumor grade were independent prognostic factors for positive ALNs. Integrating all the predictive factors, a nomogram was successfully developed and validated. The C-indexes of the nomogram for prediction of no ALN metastasis, positive ALN, and four and more ALN metastasis were 0.826, 0.706, and 0.855 in training group and 0.836, 0.731, and 0.897 in validation group. Furthermore, calibration plots and DCA demonstrated a satisfactory performance of our nomogram. CONCLUSION: We successfully construct and validate the nomogram to predict patients' axillary node status by using patients' clinicopathological and tumor characteristic factors.

A tumor microenvironment-related risk model for predicting the prognosis and tumor immunity of breast cancer patients.

Background: This study aimed to construct a tumor microenvironment (TME)-related risk model to predict the overall survival (OS) of patients with breast cancer. Methods: Gene expression data from The Cancer Genome Atlas was used as the training set. Differentially expressed gene analysis, prognosis analysis, weighted gene co-expression network analysis, Least Absolute Shrinkage and Selection Operator regression analysis, and Wald stepwise Cox regression were performed to screen for the TME-related risk model. Three Gene Expression Omnibus databases were used to validate the predictive efficiency of the prognostic model. The TME-risk-related biological function was investigated using the gene set enrichment analysis (GSEA) method. Tumor immune and mutation signatures were analyzed between low- and high-TME-risk groups. The patients' response to chemotherapy and immunotherapy were evaluated by the tumor immune dysfunction and exclusion (TIDE) score and immunophenscore (IPS). Results: Five TME-related genes were screened for constructing a prognostic signature. Higher TME risk scores were significantly associated with worse clinical outcomes in the training set and the validation set. Correlation and stratification analyses also confirmed the predictive efficiency of the TME risk model in different subtypes and stages of breast cancer. Furthermore, immune checkpoint expression and immune cell infiltration were found to be upregulated in the low-TME-risk group. Biological processes related to immune response functions were proved to be enriched in the low-TME-risk group through GSEA analysis. Tumor mutation analysis and TIDE and IPS analyses showed that the high-TME-risk group had more tumor mutation burden and responded better to immunotherapy. Conclusion: The novel and robust TME-related risk model had a strong implication for breast cancer patients in OS, immune response, and therapeutic efficiency.

Exosomal microRNA-551b-3p from bone marrow-derived mesenchymal stromal cells inhibits breast cancer progression via regulating TRIM31/Akt signaling.

Mesenchymal stromal cells (MSCs) play an important role in the development of human cancer. Meanwhile, exosomes released by MSCs can mediate cell-cell communication by delivering microRNAs (miRNAs/miRs). Hence, this study aimed to explore the role of bone marrow mesenchymal stromal cell (BMSC)-derived exosomal miR-551b-3p in breast cancer. In this study, we found that upregulation of miR-551b-5p suppressed the proliferation and migration and induced the apoptosis of breast cancer cells via downregulating tripartite motif-containing protein 31 (TRIM31). In addition, miR-551b-5p could be transferred from BMSCs to breast cancer cells via exosomes; BMSC-derived exosomal miR-551b-3p suppressed the proliferation and migration and promoted the apoptosis and oxidative stress of MDA-MB-231 cells via inhibiting TRIM31. Furthermore, a xenograft mouse model was used to explore the role of BMSC-derived exosomal miR-551b-3p in vivo. We found that BMSC-derived exosomal miR-551b-3p inhibited tumor growth in a mouse xenograft model of breast cancer in vivo. Collectively, these findings indicated that BMSC-derived exosomal miR-551b-3p could suppress the development of breast cancer via downregulating TRIM31. Thus, miR-551b-3p could serve as a potential target for the treatment of breast cancer.

Tumor infiltrating neutrophil might play a major role in predicting the clinical outcome of breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: This study was aimed to explore the predictive ability of tumor infiltrating neutrophil (TIN) in patients with breast cancer treated with neoadjuvant chemotherapy (NACT). Furthermore, the significance of TIN's dynamic change before and after NACT was investigated. METHODS: Between January 2004 and December 2017, a total of 133 patients with breast cancer who underwent NACT before surgery were enrolled in this retrospective cohort. Eighty-nine of them were able to get the core needle biopsy (CNB) samples and all the pathological samples after surgery were available. TIN was detected by immunohistochemical staining of CD66b. The optimal cut-off value was determined via receiver operating characteristic (ROC) curve analysis. The association of clinicopathologic characteristics and chemotherapy efficiency was analyzed using X2 test or Fisher's exact test or t-test as appropriate, and the prognostic significances were assessed by univariate and multivariate analyses. RESULTS: Patients with higher TIN after NACT were confirmed to be significantly associated with worse prognosis (P = 0.002). After stratifying patients into two groups, high difference group was prone to have better chemotherapy efficiency (P < 0.001) and clinical outcome in both univariate (P = 0.002) and multivariate analyses (P = 0.003). CONCLUSIONS: In this study, higher TIN after NACT was confirmed to be associated with breast cancer patients' worse chemotherapy efficiency and shorter disease-free survival (DFS). Furthermore, the TIN's dynamic change before and after NACT was firstly proved to be a more accurate predictive marker compared with TIN after NACT.

MORC4 is a novel breast cancer oncogene regulated by miR-193b-3p.

A better understanding of breast cancer pathogenesis would contribute to improved diagnosis and therapy and potentially decreased mortality rates. Here, we found that the MORC family CW-type zinc finger 4 (MORC4) overexpression in breast cancer tissues is associated with poor survival, and the short-interfering RNA knockdown of MORC4 suppresses the growth of breast cancer cells by promoting apoptosis. To investigate the mechanisms associated with MORC4 upregulation, microRNAs potentially targeting MORC4 were analyzed, with miR-193b-3p identified as the regulator and a negative correlation between miR-193b-3p and MORC4 expression determined in both breast cancer cell lines and tissues. Further analysis verified that MORC4 silencing did not affect miR-193b-3p expression, although altered miR-193b-3p expression attenuated MORC4 protein levels. Moreover, dual-luciferase reporter assays verified miR-193b-3p binding to the 3' untranslated region of MORC4. Furthermore, restoration of miR-193b-3p expression in breast cancer cells led to decreased growth and activation of apoptosis, which was consistent with results associated with MORC4 silencing in breast cancer cells. These results identified MORC4 as differentially expressed in breast cancer cells and tissues and its downregulation by miR-193b-3p, as well as its roles in regulating the growth of breast cancer cells via regulation of apoptosis. Our findings offer novel insights into potential mechanisms associated with breast cancer pathogenesis.

Neutrophil to lymphocyte ratio is a prognostic factor for disease free survival in patients with breast cancer underwent curative resection.

The aim of this study was to explore the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) in patients with breast cancer after curative resection. Furthermore, we aimed to confirm the prognostic significance of NLR in early stage and different molecular types of breast cancer, as well as patients treated with neoadjuvant chemotherapy (NACT).A total of 2458 patients between January 2002 and December 2014 from 2 independent cohorts were analyzed retrospectively. The optimal cut-off value of NLR for recurrence was determined via receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were used to assess the relationship between NLR and disease-free survival (DFS).Both univariate and multivariate analysis showed that patients with high NLR were more inclined to suffer postoperative recurrence in 2 independent cohorts. NLR was identified as independent prognostic factor for DFS of early stage breast cancer (P < .05), different types of breast cancer (P < .05) and patients treated with NACT (P < .05).Our data suggest NLR is independent prognostic factor for breast cancer patients. In addition, the prognostic value of NLR was further confirmed in early stage and different molecular types of breast cancer as well as patients treated with NACT.