1.Tumor-associated macrophages affect breast cancer endocrine resistance through FOXM1/Wnt/ β-catenin pathway
Qilong ZHAO ; Zejie SHAO ; Qingshan MA ; Xin WANG ; Changxin LYU
Chinese Journal of Endocrine Surgery 2023;17(4):484-489
Objective:To explore the influence of tumor-associated macrophages (TAMs) on endocrine resistance in breast cancer through the forkhead box M1 (FOXM1) /Wnt/ β-catenin pathway. Methods:Tamoxifen-resistant breast cancer cells were cultured, THP-1 cells were induced into macrophages (MΦ), and further induced into TAMs. After being cultured in the conditioned medium (CM) of MCF-7 cells for 24 hours, MΦ were defined as MS cells. After being cultured in the CM of MCF-7R cells for 24 hours, MΦ were defined as MR cells. MCF-7 cells, after being cultured in the CM of macrophages for 24 hours, were defined as MCF-7 (MΦ) cells. MCF-7 cells, after being cultured in the CM of MS cells for 24 hours, were defined as MCF-7 (MS) cells. MCF-7 cells, after being cultured in the CM of MR cells for 24 hours, were defined as MCF-7 (MR) cells. Cell viability and invasion ability were evaluated using CCK-8 and Transwell assays. The protein levels of CD163, Wnt1, β-catenin, and FOXM1 in different groups were examined by qRT-PCR and Western blot. Results:Compared to the MS group (mRNA: 1.49±0.12, protein: 1.15±0.12), CD163 expression was higher in the MR group (mRNA: 2.33±0.16, protein 1.52±0.11) ( t=7.28, P=0.002) ( t=3.94, P=0.017), indicating that tamoxifen-resistant breast cancer cells can induce polarization of more MΦ into TAMs. TAMs increased the expression of FOXM1 in breast cancer cells, which further activated the Wnt/ β-catenin pathway. Compared to the MCF-7 (MΦ) group, the MCF-7 (MS) and MCF-7 (MR) groups showed enhanced cell viability and invasion, with the most significant increase observed in the MCF-7 (MR) group. Compared with MCF-7 (MΦ) cells, the levels of Wnt1, β-catenin, and FOXM1 in MCF-7 (MS) and MCF-7 (MR) cells were significantly increased, with the highest levels observed in the MCF-7 (MR) group with the most TAM polarization. Compared to the MCF-7 group, both the MCF-7 (MR) and MCF-7+pcDNA-FOXM1 groups showed increased levels of Wnt1 and β-catenin, enhanced cell viability and invasion. Compared to the MCF-7 (MR) group, the MCF-7 (MR) + si-FOXM1 group showed reduced levels of Wnt1 and β-catenin, weakened cell viability and invasion. Conclusion:TAMs promote endocrine resistance in breast cancer by upregulating FOXM1 and activating the Wnt/ β-catenin pathway.
2.Construction of a predictive model based on columnar maps for factors influencing lesion residuals after minimally invasive rotary mastectomy for breast masses
Changxin LYU ; Zejie SHAO ; Li LI ; Liyong FENG ; Shengjie MA ; Cuili LIU
Chinese Journal of Endocrine Surgery 2023;17(1):84-89
Objective:To investigate the influencing factors associated with lesion residual after minimally invasive rotary mastectomy for breast masses and to construct a predictive model using columnar plots.Methods:Two hundred and twenty-eight patients with Breast lumps in Linyi People’s Hospital from Jun. 2018 to Jun. 2020 were selected as study subjects, all of whom underwent minimally invasive rotational resection, and the influencing factors of postoperative lesion residual were analyzed using univariate and multifactorial analysis, and a column line graph risk warning model was constructed and given for evaluation and validation.Results:228 patients were followed up for 6 months after surgery, 3 cases were lost, 225 cases completed postoperative follow-up, among which 185 cases (82.22%) had successfully resected lesions; 40 cases (17.78%) had residual lesions. Univariate, logistic regression analysis showed that tumor diameter ( t=15.52, P<0.001) , lesion morphology ( t=15.52, P<0.001) , lesion boundary ( χ2=7.71, P=0.006) , ultrasound guidance ( χ2=12.69, P<0.001) , and minimally invasive spinotomy system ( χ2=10.64, P=0.001) were the factors influencing lesion residual after minimally invasive spinotomy of breast masses. Based on the above factors to construct a column line graph model of lesion residual after minimally invasive rotational mastectomy for breast lumps, the area under the working characteristic curve (ROC) for model subjects was 0.974 (95% CI: 0.954-0.994) , indicating that the calibration curve basically matched the actual curve; external validation of the model showed that the area under the obtained ROC was 0.962 (95% CI: 0.933-0.991) , indicating that the model has a high degree of calibration. Conclusion:Tumor diameter, lesion morphology, lesion boundary, ultrasound guidance, and minimally invasive spinotomy system are the influencing factors of lesion residual after minimally invasive spinotomy for Breast lumps, and the column line graph model prediction of lesion residual occurring after surgery constructed based on the above factors has good confidence.