生存素乳腺癌耐药蛋白和人表皮生长因子受体2基因的表达与乳腺癌新辅助化疗疗效的关系

目的 探讨生存素(Survivin)、乳腺癌耐药蛋白(BCRP)以及人表皮生长因子受体2(HER-2)基因表达对乳腺癌TE方案新辅助化疗疗效的预测价值.方法 对56例乳腺癌患者行TE方案新辅助化疗,应用RT-PCR法检测TE方案化疗前后Survivin、BCRP和HER-2 mRNA的表达差异,并结合化疗疗效进行相关性分析.结果 56例乳腺癌患者经TE方案新辅助化疗后的总有效率为71.4％.全组完全缓解5例,病理完全缓解4例,部分缓解35例,稳定13例,进展3例.Survivin mRNA的阳性表达率由化疗前的60.7％降至化疗后的35.7％ (P =0.008);BCRP mRNA的阳性表达率由化疗前的37.5％降至化疗后的19.6％(P=0.036);HER-2 mRNA的阳性表达率由化疗前的41.1％降至化疗后的21.4％ (P =0.025).Survivin或BCRP单独阴性表达的患者化疗的有效率均较阳性表达者高(均P＜0.05).HER-2 mRNA的单独表达状况与化疗疗效无关(P =0.144).Survivin、BCRP和HER-2 mRNA均为阴性表达的患者化疗疗效高于其他各组(P =0.003).在乳腺癌组织中,Survivin、BCRP和HER-2 mRNA的表达之间不存在相关关系(P＞0.05).结论 联合检测Survivin、BCRP和HER-2的表达可作为预测乳腺癌TE方案新辅助化疗敏感性的分子生物学指标.

Correlation of expression of Survivin, BCRP and HER-2 genes with therapeutic response of TE regimen neoadjuvant chemotherapy in breast cancer patients

Objective To study the changes of expression of Survivin mRNA,BCRP mRNA and HER-2 mRNA in breast cancer after TE regimen neoadjuvant chemotherapy,and to find biological markers to predict the efficiency of TE regimen neoadjuvant chemotherapy. Methods The gene expressions were detected by RT-PCR from 56 breast cancer patients before and after TE regimen neoadjuvant chemotherapy (docetaxel and epirubicin).The relationships between these gene expressions and chemotherapy responses were analyzed.Results The overall response rate to neoadjuvant chemotherapy was 71.4％,including 8.9％ (5/56) with complete response and 62.5％ (35/56) with partial response.Pathological complete response was found in 4 cases (7.1％ ).Stable disease and progression of disease were 23.2％ (13/56) and 5.4％ (3/56),respectively.The expression of Survivin mRNA after neoadjuvant chemotherapy was 35.7％ (20/56),significantly lower than 60.7％ (34/56) before neoadjuvant chemotherapy (P =0.008 ).The expression of BCRP mRNA after neoadjuvant chemotherapy was 19.6％,significantly lower than 37.5％before neoadjuvant chemotherapy (P =0.036).The positive rate of HER-2 mRNA expression was 41.1％ before the chemotherapy,and reduced to 21.4％ after the chemotherapy ( P =O.025 ).The effective rates of the single positive expression of Survivin mRNA or BCRP mRNA were both lower than that of negative expression ( P ＜0.05 ).The level of HER-2 mRNA expression alone was not significantly associated with the effective rate of chemotherapy (P =0.144).When the expression of all Survivin mRNA,BCRP mRNA and HER-2 mRNA were negative,the effective rate of neoadjuvant chemotherapy was higher than that in patients with positive expression ( P =0.003 ). The level of Survivin mRNA expression was not significantly associated with BCRP mRNA and HER-2 mRNA (P ＞ 0.05).Conclusion The expression of Survivin in combination with BCRP and HER-2 is associated with clinical response to TE neoadjuvant chemotherapy in breast cancer,and can be used as predictive biomarkers for chemosensitivity of TE regimen neoadjuvant chemotherapy for breast cancer.