Background: Breast cancer is a common cancer worldwide. Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer characterized by a poor prognosis. Icariin (ICA) is a flavonoid glycoside purified from the natural product Epimedium, which is reported to exert an inhibitory effect on a variety of cancers. However, molecular mechanisms behind ICA suppressed TNBC remain elusive. Methods:The curative effects of ICA on TNBC cells and potential targets were predicted by network pharmacology and molecular biology methods screening, and the mechanism of inhibition was explained through in vitro experiments such as cell function determination, Western blot analysis, molecular docking verification, etc. Results: This study showed that ICA inhibits TNBC cell functions such as proliferation, migration, and invasion in a dose-dependent manner. ICA could induce redox-induced apoptosis in TNBC cell, as shown by ROS upregulation. As a result of network pharmacology, ICA was predicted to be able to inhibit the MAPK signaling pathway. ICA treatment inhibited the expression of JNK and c-Jun and downregulated the antiapoptotic gene cIAP-2. Our results suggested that ICA could induce apoptosis by inducing an excessive accumulation of ROS in cells and suppress TNBC cell invasion via the JNK/c-Jun signaling pathway. Conclusion:We demonstrated that ICA can effectively inhibit cell proliferation and induced apoptosis of TNBC cells. In addition, ICA could inhibit TNBC cell invasion through the JNK/c-Jun signaling pathway. The above suggests that ICA may become a potential drug for TNBC.

Background Evidence of the association between psychiatric disorders, and breast cancer have been inconsistent, and their interpretation often encounters confounding factors. In this study, we used bidirectional Mendelian randomization (MR) analysis to explore the genetic relationships between them. Methods We performed an MR analysis using publicly available genome-wide association studies of European ancestry to simultaneously examine the relationship between psychiatric disorders, and breast cancer risk. The inverse-variance weighted method for the assessment of the risk psychiatric disorders bring to breast cancer. Weighted media, and MR-Egger regression were used as sensitivity analyses. Results The MR analysis revealed that major depressive disorder (MDD) may increase the risk of overall breast cancer (odds ratio [OR] = 1.095, 95% confidence interval [CI] = 1.019-1.277, P = 0.014), but not the subtype of breast cancer. Schizophrenia (SCZ) was a risk factor for overall breast cancer (OR = 1.031, 95%CI = 1.012-1.050, P = 0.002), ER+ breast cancer (OR = 1.034, 95%CI = 1.012-1.057, P = 0.002) and ER- breast cancer (OR = 1.050, 95%CI = 1.017-1.084, P = 0.003). However, patients with breast cancer are less likely to have the risk of MDD and SCZ. Conclusion: Our results found that MDD may be a risk factor for overall breast cancer but is not related to its subtypes. SCZ may increase the risk of breast cancer and its subtypes.

PurposeWe aimed at establishing a nomogram to accurately predict the overall survival (OS) of non-metastatic invasive micropapillary breast carcinoma (IMPC).MethodsIn the training cohort, data from 429 patients with non-metastatic IMPC were obtained through the Surveillance, Epidemiology, and End Results (SEER) database. Other 102 patients were enrolled at the Xijing Hospital as validation cohort. Independent risk factors affecting OS were ascertained using univariate and multivariate Cox regression. A nomogram was established to predict OS at 3, 5 and 8 years. The concordance index (C-index), the area under a receiver operating characteristic (ROC) curve and calibration curves were utilized to assess calibration, discrimination and predictive accuracy. Finally, the nomogram was utilized to stratify the risk. The OS between groups was compared through Kaplan-Meier survival curves.ResultsThe multivariate analyses revealed that race (p = 0.047), surgery (p = 0.003), positive lymph nodes (p = 0.027), T stage (p = 0.045) and estrogen receptors (p = 0.019) were independent prognostic risk factors. The C-index was 0.766 (95% CI, 0.682-0.850) in the training cohort and 0.694 (95% CI, 0.527-0.861) in the validation cohort. Furthermore, the predicted OS was consistent with actual observation. The AUCs for OS at 3, 5 and 8 years were 0.786 (95% CI: 0.656-0.916), 0.791 (95% CI: 0.669-0.912), and 0.774 (95% CI: 0.688-0.860) in the training cohort, respectively. The area under the curves (AUCs) for OS at 3, 5 and 8 years were 0.653 (95% CI: 0.498-0.808), 0.683 (95% CI: 0.546-0.820), and 0.716 (95% CI: 0.595-0.836) in the validation cohort, respectively. The Kaplan-Meier survival curves revealed a significant different OS between groups in both cohorts (p<0.001).ConclusionOur novel prognostic nomogram for non-metastatic IMPC patients achieved a good level of accuracy in both cohorts and could be used to optimize the treatment based on the individual risk factors.

Purpose We aimed at establishing a nomogram to accurately forecast the overall survival (OS) of non-metastatic invasive micropapillary breast carcinoma (IMPC). Methods In the training cohort, data from 429 patients with non-metastatic IMPC were obtained through the Surveillance, Epidemiology, and End Results (SEER) database. Other 102 patients were enrolled at the Xijing Hospital as validation cohort. Independent risk factors affecting OS were ascertained using univariate and multivariate Cox regression. A nomogram was established to forecast OS at 3, 5 and 8 years. The concordance index (C-index), the area under a receiver operating characteristic (ROC) curve and calibration curves were utilized to assess calibration, discrimination and predictive accuracy. Finally, the nomogram was utilized to stratify the risk. The OS between groups was compared through Kaplan-Meier survival curves. Results The multivariate analyses revealed that race (p = 0.047), surgery (p = 0.003), positive lymph nodes (p = 0.027), T stage (p = 0.045) and estrogen receptors (p = 0.019) were independent prognostic risk factors. The C-index was 0.766 (95% CI, 0.682–0.850) in the training cohort and 0.694 (95% CI, 0.527–0.861) in the validation cohort. Furthermore, the predicted OS was consistent with actual observation. The AUCs for OS at 3, 5 and and 8 years were 0.786 (95% CI: 0.656–0.916), 0.791 (95% CI: 0.669–0.912), and 0.774 (95% CI: 0.688–0.860) in the training cohort, respectively. The area under the curves (AUCs) for OS at 3, 5 and 8 years were 0.653 (95% CI: 0.498–0.808), 0.683 (95% CI: 0.546–0.820), and 0.716 (95% CI: 0.595–0.836) in the validation cohort, respectively. The Kaplan-Meier survival curves revealed a significant different OS between groups in both cohorts (p༜0.001). Conclusion Our novel prognostic nomogram for non-metastatic IMPC patients achieved a good level of accuracy in both cohorts and could be used to optimize the treatment based on the individual risk factors.