Network pharmacology and experimental validation to reveal the pharmacological mechanisms of Qizhu prescription for treating breast cancer

Objective:To investigate the mechanism underlying the effects exerted by the Qizhu prescription(QZP)in breast cancer(BC),and the respective targets.Methods: Expression data from the ArrayExpress and The Cancer Genome Atlas(TCGA)were used to identify differentially expressed genes(DEGs)in BC.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on the DEGs to identify genes involved in protein–protein interactions.Molecular docking was used to explore the dynamic relationship between active molecules and targets.Cell function experiments and animal studies were conducted to evaluate the effects of hub genes and active QZP compounds on BC cell behavior.Results: Among the 25 evaluated BC-related targets of QZP,matrix metalloproteinase-1(MMP1)and epidermal growth factor receptor(EGFR)exhibited the highest degrees of dysregulation.GO and KEGG enrichment analyses revealed that the anti-BC targets of QZP primarily affected drug responses and pathways in cancer cells.Molecular docking analysis suggested potential interactions between EGFR and quercetin/luteolin,as well as between MMP1 and luteolin/kaempferol/quercetin.Quercetin significantly reduced BC cell proliferation,migration,invasion,and tumor development in vivo.Treatment of BC cells with quercetin decreased the expression or activation of several associated proteins.Conclusion: The findings of our study provide new insights into the therapeutic potential of traditional Chinese medicine against BC,with particular reference to QZP.

CD14 macrophage and IL-10 levels in the peripheral blood of breast cancer patients and their diagnostic value

Objective To explore the correlation between macrophages and interleukin-10(IL-10 in the peripheral blood of breast cancer(BC)patients and the diagnostic value of joint detection.Methods BC patients(n=50)and healthy controls(n=40)were prospectively recruited.The percentage of circulating cluster of differentiation 14(CD 14)macrophage cells was analyzed by flow cytometry,and an enzyme-linked immunosorbent assay(ELISA)was used to detect IL-10 expression levels.Receiver operating characteristic(ROC)curves were used to verify the diagnostic value of the models based on the expression of CD14 macrophage cell populations and IL-10.In addition,the association between model expression and clinicopathological characteristics was investigated.Another 30 patients with BC and 30 with benign breast disease were selected to validate the IL-10 and CD14 macrophage joint detection model using the same method.Results CD14 macrophage and IL-10 expression levels in BC patients were higher than those in healthy controls(P<0.05).The ROC curve showed that the area under the curve(AUC)of CD14+macrophages combined with IL-10 was 0.830,the sensitivity was 72.0%,and the specificity was 87.5%.Its diagnostic efficiency was better than all other single and joint detections.Correlation analysis of clinicopathological features showed that IL-10 and CD14+macrophage joint detection was significantly correlated with tumor size,tumor-node-metastasis(TNM)stage,and lymph node,estrogen receptor(ER),and Ki-67 expression(P<0.05).The validation analysis results were consistent with the test results.Conclusion Peripheral blood macrophages can be an independent diagnostic marker for BC.Joint detection of CD14-macrophages and IL-10 suggests poor prognosis,which has unlimited potential to guide BC development and provides a new theory for studying tumor-associated macrophages in BC.

KIF15 expression characteristics: Relevance toneo-adjuvant chemotherapy efficacy in breast cancer

Objective The relationship between the expression of kinesin family member 15 (KIF15) andclinicopathological features in breast cancer (BC) remains controversial. In this study, we aimed to explorethe influence of KIF15 expression on the efficacy of neoadjuvant chemotherapy (NAC) and evaluate itsclinical value in predicting prognosis for BC patients.Methods Immunohistochemistry was used to detect KIF15 expression in 93 BC patients undergoingNAC to analyze the relationship between KIF15 expression and clinical efficacy and analytical parameters.Results Of the 93 BC patients enrolled, 24.73% who underwent NAC had higher KIF15 expression levels,showing positive correlations with ER, HER-2, Ki67, and lymph node metastasis (P < 0.05). The clinicalbenefit of NAC was 70.97%, and the major histological response (MHR) rate was 61.29%. The effectivetherapeutic rate in patients with high KIF15 expression was 95.65%, while the MHR rate was 65.22%.Various molecular BC subtypes with varied clinical and pathological responses exhibited correlation toa large extent. Of all the BC patients studied, 84% of the triple-negative breast cancer (TNBC) patientswere evaluated as clinically effective, and 52% of the TNBC patients were evaluated as pathologicallyeffective, and these values were significantly higher than those of the other molecular types (P < 0.05).The expression of KIF15 in 25 TNBC patients showed positive correlations with lymph node metastasis.Conclusion Overexpression of KIF15 was shown to increase BC sensitivity to chemotherapy anddemonstrated better outcomes.