血浆微泡乳腺癌耐药蛋白mRNA水平对乳腺癌化疗疗效的预测价值

The clinical values of breast cancer resistance protein mRNA levels in plasma microvesicles predicting breast cancer chemotherapy

目的 探讨乳腺癌患者外周血微泡（MVs）携带乳腺癌耐药相关蛋白（BCRP） mRNA水平对化疗疗效的预测价值.方法 分别采用免疫荧光技术、实时定量反转录聚合酶链反应（RT-qPCR）技术对40例乳腺癌辅助化疗患者（BC组）、84例转移性乳腺癌姑息化疗患者（mBC组）及40例正常体检女性（NF组）血浆微泡黏蛋白1（MUC1）、BCRP表达率以及BCRP mRNA水平进行检测;应用Kaplan-Meier法和Cox多因素回归模型分析临床病理参数、BCRP mRNA水平与化疗疗效的关系.结果 BC组和mBC组MUC1表达率分别为（11.60±0.76）％、（6.67±1.03）％（P＜0.05）,MUC1、BCRP共表达率分别为（14.06 ±0.62）％、（1.83±0.39）％（P＜0.05）.BC组和NF组的BCRP mRNA相对水平分别为-2.32±0.75和-2.15±0.66（P＞0.05）;mBC组为-5.75±0.38,显著高于BC组（P＜0.01）.按RECIST标准,mBC中完全缓解（CR）/部分缓解（PR）/稳定（SD）组和进展（PD）组血浆微泡BCRPmRNA相对水平分别为-4.03 ±0.71、-6.30±0.44（P＜0.01）;BCRP mRNA-high组的中位无进展生存期（PFS）为2.80个月,BCRP mRNA-low组中位PFS为4.00个月（P＜0.01）.Cox回归分析显示：血浆微泡BCRP mRNA水平是晚期转移性乳腺癌化疗的独立不良预后因素（P＜0.05）.结论 血浆微泡BCRP mRNA水平可能是预测乳腺癌患者化疗疗效的潜在标志物.

Objective To investigate the predictive values of peripheral blood microvesicles （MVs） containing breast cancer resistance protein （BCRP） mRNA on chemotherapy effectiveness in breast cancer.Methods We selected 40 cases of breast cancer （BC） chemotherapy,84 cases of palliative chemotherapy in patients with advanced metastatic breast cancer （mBC）,and 40 cases of normal volunteers （NF）.Immunofluorescence was used to detect mucin 1 （MUC1） expression rate and co-expression rate of MUC1 and BCRP in plasma MVs.Real-time quantitative reverse transcriptase-polymerase chain reaction （RT-qPCR） was used to detect BCRP mRNA level in plasma MVs.The correlations between clinicopathologic features and BCRP mRNA level with chemotherapy effectiveness were analyzed by the Kaplan-Meier method and Cox regression.Results MUC1 expression rate and co-expression rate of MUC1 and BCRP in plasma MVs of mBC group were （11.60 ± 0.76） % and （14.06 ± 0.62） %,and those in BC group were （6.67 ± 1.03） % and （1.83 ± 0.39） % （P 〈 0.05）.The BCRP mRNA relative levels of plasma MVs in NF,BC and mBC groups were-2.15 ±0.66,-2.32 ±0.75,and-5.75 ±0.38 respectively.The BCRP mRNA relative levels of plasma MVs in mBC group was significantly higher than in BC group （P 〈0.01）.According to Response Evaluation Criteria in solid tumors,mBC group was subdivided into the stable disease （SD） subgroup and disease control （DCR） [complete remission （CR）/partial remission （PR）/SD] subgroup.BCRP mRNA relative levels in plasma MVs of SD subgroup and DCR subgroup were -4.03±0.71,and-6.30 ±0.44 respectively with the difference being statistically significant （P 〈0.01）.The median progression-free survival （mPFS） on high and low BCRP mRNA expression groups was 2.80 and 4.00 months respectively （P 〈 0.01）.Cox regression analysis showed BCRP mRNA level in the plasma MVs was an independent prognostic factor in advanced metastatic breast cancer chemotherapy （P 〈 0.05）.Conclusion The BCRP mRNA levels in the plasma MVs may predict the response of breast cancer chemotherapy as potential markers.