HOPX表达与局部晚期乳腺癌新辅助化疗疗效的关系

Relationship between HOPX expression and efficacy of neoadjuvant chemotherapy for patients with locally advanced breast cancer

目的探讨局部晚期乳腺癌组织中同源域蛋白同源盒(HOPX)表达及外周血HOPX甲基化与新辅助化疗疗效的关系。方法回顾性分析2020年1月至2023年10月咸阳市中心医院收治的129例局部晚期乳腺癌患者的资料,年龄(50.69±5.48)岁;中高分化71例、低分化58例;ⅡB期48例、Ⅲ期81例;淋巴结转移87例。根据新辅助化疗疗效分为病理完全缓解(pCR)、非pCR。检测患者新辅助化疗前癌组织、癌旁组织中HOPX表达及外周血HOPX甲基化水平。分析局部晚期乳腺癌患者癌组织中HOPX表达、外周血HOPX甲基化率表达与病理特征关系,影响化疗疗效的因素,癌组织中HOPX mRNA相对表达量、外周血HOPX甲基化率预测局部晚期乳腺癌患者新辅助化疗疗效的价值。采用t检验、χ^(2)检验,影响因素用Cox比例风险模型,受试者操作特征曲线(ROC)评估预测效能。结果癌组织中HOPX mRNA相对表达量高于癌旁组织[(1.97±0.32)比(1.13±0.21),P<0.05]。低分化、Ⅲ期、有淋巴结转移的患者癌组织中HOPX mRNA相对表达量、外周血HOPX甲基化率分别高于中高分化、ⅡB期、无淋巴结转移者[(2.19±0.37)比(1.79±0.32)、(2.23±0.39)比(1.53±0.26)、(2.14±0.35)比(1.62±0.28),81.03%(47/58)比56.34%(40/71)、75.31%(61/81)比54.17%(26/48)、73.56%(64/87)比54.76%(23/42),均P<0.05]。Cox回归分析显示:肿瘤分期(RR=5.557,95%CI:2.286~13.505)、分化程度(RR=5.360,95%CI:2.206~13.027)、HOPX mRNA相对表达量(RR=4.455,95%CI:1.833~10.827)、HOPX甲基化率(RR=4.362,95%CI:1.795~10.602)是影响局部晚期乳腺癌患者新辅助化疗疗效的因素(均P<0.05)。ROC分析结果显示,HOPX mRNA相对表达量联合HOPX甲基化率预测局部晚期乳腺癌患者新辅助化疗疗效的曲线下面积高于单独预测(0.894比0.774比0.768)。结论局部晚期乳腺癌患者癌组织中HOPX mRNA相对表达量、外周血HOPX甲基化率与病理特征、新辅助化疗疗效相关,二者联合预测患者新辅助化疗疗效的效能良好。

Objective To investigate the relationship of the expression of homologous domain protein homeobox(HOPX)and the methylation of HOPX in peripheral blood with the efficacy of neoadjuvant chemotherapy for patients with locally advanced breast cancer.Methods The data of 129 patients admitted to Xianyang Central Hospital were analyzed.They were(50.69±5.48)years old.There were 71 cases of high differentiation and 58 cases of low differentiation.There were 48 cases of stageⅡB and 81 cases of stageⅢ.Eighty-seven cases had lymph node metastasis.According to the efficacy of neoadjuvant chemotherapy,they were divided into pathological complete response(pCR)and non-pCR.The expression of HOPX and the methylation level of HOPX in peripheral blood in the patients before neoadjuvant chemotherapy were detected.The relationship of HOPX expression in cancer tissue and HOPX methylation rate in peripheral blood with the pathological features of the patients with locally advanced breast cancer was analyzed.The factors influencing the efficacy of neoadjuvant chemotherapy were analyzed.The relative expression of HOPX mRNA in cancer tissue and the methylation rate of HOPX in peripheral blood in predicting the efficacy of neoadjuvant chemotherapy for the patients were analyzed.t andχ^(2)tests were used.The Cox proportional risk model was used for the influencing factors.The receiver operating characteristic curve(ROC)was used to evaluate the prediction efficacy.Results The relative expression level of HOPX mRNA in the cancer tissue was higher than that in the adjacent tissue[(1.97±0.32)vs.(1.13±0.21);P<0.05].The relative expression level of HOPX mRNA and the methylation rate of HOPX in peripheral blood of the patients with low differentiation,stageⅢ,and lymph node metastasis were higher than those of the patients with middle and high differentiation,stageⅡB,and no lymph node metastasis[(2.19±0.37)vs.(1.79±0.32),(2.23±0.39)vs.(1.53±0.26),(2.14±0.35)vs.(1.62±0.28),81.03%(47/58)vs.56.34%(40/71),75.31%(61/81)vs.54.17%(26/48),and 73.56%(64/87)vs.54.76%(23/42);all P<0.05].The Cox regression analysis showed that tumor stage(RR=5.557,95%CI 2.286-13.505),differentiation degree(RR=5.360,95%CI 2.206-13.027),relative expression level of HOPX mRNA(RR=4.455,95%CI 1.833-10.827),and HOPX methylation rate(RR=4.362,95%CI 1.795-10.602)were the factors affecting the efficacy of neoadjuvant chemotherapy for the patients(all P<0.05).The ROC analysis results showed that the relative expression level of HOPX mRNA combined with HOPX methylation rate had AUC in predicting the efficacy of neoadjuvant chemotherapy for the patients than single one(0.894 vs.0.774 and 0.894 vs.0.768).Conclusions The relative expression level of HOPX mRNA in cancer tissue and the methylation rate of HOPX in peripheral blood of patients with locally advanced breast cancer are closely related to pathological characteristics and the efficacy of neoadjuvant chemotherapy.The combination of the two can predict the efficacy of neoadjuvant chemotherapy well.