摘要目的:分析Hippo信号通路在三阴性乳腺癌(TNBC)细胞上皮-间质转化(EMT)中的作用。方法:选取延安市人民医院2021年4月—2023年9月收治的70例TNBC患者，于治疗前采用实时荧光定量聚合酶链式反应(qRT-PCR)检测外周血中Hippo信号通路相关指标(Yap、ta Z、mst 1)mRNA表达水平，给予患者TP方案治疗21 d。治疗后对患者肿瘤组织行穿刺活检，根据是否发生EMT将其分为转化组和非转化组，分析TNBC患者肿瘤细胞发生EMT的影响因素及分析Hippo信号通路预测TNBC患者肿瘤细胞发生EMT的价值。结果:70例TNBC患者经治疗后，发生EMT 18例(25.71%)。转化组TNM分期Ⅳ期比例(13/18)、Yap mRNA水平(4.82±0.63)、ta Z mRNA水平(2.93±0.41)、mst 1 mRNA水平(3.09±0.51)、肿瘤长径[(5.95±0.77)cm]均高于非转化组[44.23%(23/52)、(3.84±0.59)、(2.34±0.39)、(2.45±0.47)、(4.14±0.63)cm](均 P<0.05)。经二元logistic回归分析，发现TNM分期Ⅳ期[ OR＝4.768，95% CI(1.630，13.951)]、Yap mRNA[ OR＝5.675，95% CI(1.940，16.602)]、ta Z mRNA[ OR＝5.124，95% CI(1.751，14.992)]、mst 1 mRNA[ OR＝5.557，95% CI(1.899，16.257)]、肿瘤长径[ OR＝3.850，95% CI(1.316，11.263)]是TNBC患者肿瘤细胞发生EMT的影响因素(均 P<0.05)。经受试者工作特征(ROC)曲线分析，TNM分期为Ⅳ期、Yap mRNA、ta Z mRNA、mst 1 mRNA、肿瘤长径、五者联合预测TNBC患者肿瘤细胞发生EMT的灵敏度分别为66.67%、72.22%、77.78%、72.22%、77.78%、88.89%；特异度分别为69.23%、71.15%、76.92%、73.08%、75.00%、92.31%。TNM分期Ⅳ期、Yap mRNA、ta Z mRNA、mst 1 mRNA、肿瘤长径五者联合预测TNBC患者肿瘤细胞发生EMT的价值较高(均 P<0.05)。 结论:TNM分期Ⅳ期、Yap mRNA、ta Z mRNA、mst 1 mRNA、肿瘤长径联合检测能更好地预测TNBC患者肿瘤细胞EMT的发生。

abstractsObjective:To analyze the role of the Hippo signaling pathway in epithelial-mesenchymal transition (EMT) of triple-negative breast cancer (TNBC) cells.Methods:70 patients with TNBC admitted to the Yan ′an People′s Hospital from April 2021 to September 2023 were selected. Before treatment, real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of Hippo signaling pathway-related indicators (Yap, ta Z, mst 1) in peripheral blood, and the patients were treated with the TP regimen for 21 days. After the treatment, puncture biopsy was performed on the tumor tissues of the patients. They were divided into the transformation group and the non-transformation group based on whether EMT occurred. The influencing factors of EMT in tumor cells of TNBC patients were analyzed, and the value of the Hippo signaling pathway in predicting EMT in tumor cells of TNBC patients was analyzed.Results:After treatment, 18 cases (25.71%) of 70 patients with TNBC developed EMT. The proportion of tumor node metastasis (TNM) stage Ⅳ in the transformation group was (13/18), the level of Yap mRNA was (4.82±0.63), the level of taZ mRNA was (2.93±0.41), and the mst 1 mRNA level (3.09±0.51) and the long diameter of the tumor [(5.95±0.77)cm] were both higher than those in the non-transformation group [44.23%(23/52), (3.84±0.59), (2.34±0.39), (2.45±0.47), (4.14±0.63)cm] (all P<0.05). Binary logistic regression analysis revealed TNM stage Ⅳ [ OR=4.768, 95% CI(1.630, 13.951)], Yap mRNA [ OR=5.675, 95% CI(1.940, 16.602)], and taZ mRNA [ OR=5.124 95% CI(1.751, 14.992)], mst 1 mRNA [ OR=5.557, 95% CI(1.899, 16.257)], tumor long diameter [ OR=3.850, 95% CI(1.316, 11.263)] was an influencing factor for the occurrence of EMT in tumor cells of TNBC patients (all P<0.05). After analysis by the receiver operating characteristic (ROC) curve, the combined sensitivity of TNM stage Ⅳ, Yap mRNA, taZ mRNA, mst 1 mRNA, and tumor long diameter in predicting EMT in tumor cells of TNBC patients was 66.67%, 72.22%, 77.78%, 72.22%, 77.78%, and 88.89%, respectively. The specificities were 69.23%, 71.15%, 76.92%, 73.08%, 75.00% and 92.31% respectively. The combined prediction of TNM stage Ⅳ, Yap mRNA, taZ mRNA, mst 1 mRNA, and tumor long diameter in tumor cells of TNBC patients had a relatively high value (all P<0.05). Conclusions:The combined detection of TNM stage Ⅳ, Yap mRNA, taZ mRNA, mst 1 mRNA, and tumor long diameter can better predict the occurrence of EMT in tumor cells of patients with TNBC.