血清miRNA-429预测乳腺癌新辅助化疗疗效价值研究

Predictive value of serum miRNA-429 expression in neoadjuvant chemotherapy for breast cancer

目的乳腺癌新辅助化疗疗效不一,本研究通过检测血清中miRNA-429表达水平,验证其是否可以作为乳腺癌患者对TAC方案(多柔比星+多西紫衫醇+环磷酰胺)新辅助化疗临床疗效的预测指标。方法采用前瞻性研究,以2012-01-01-2016-01-31在丹阳市人民医院就诊并接受TAC方案的146例乳腺癌患者为研究对象,比较新辅助化疗前后患者血清中miRNA-429表达水平以及肿瘤组织中Ki-67、HER2、ER和PR表达差异,并分析miRNA-429表达水平对患者病理完全缓解(pCR)、无病生存期及总生存期的影响。结果根据Ki-67、HER2、ER、PR表达差异,146例乳腺癌患者可分为Luminal A型20例(14%),Luminal B型52例(36%),ER^+HER2^+型27例(18%),ER^-HER2^-型25例(17%),ER^-HER2^+型22例(15%)。治疗总有效率Luminal B型为73%,ER^+HER2^+型为100%,ER^-HER2^-型为72%,ER^-HER2^+型为77%,均高于Luminal A型的30%,差异有统计学意义,均P<0.05。乳腺癌各亚型pCR率比较,差异无统计学意义,U=8.919,P=0.063。乳腺癌各亚组在给与TAC方案前后血清中miRNA-429表达水平差异均无统计学意义,均P>0.05。根据新辅助化疗后病灶残留分组,pCR患者的miR-429相对表达量为3.34±0.47,低度病灶残留为2.58±0.35,中度病灶残留为1.28±0.36,重度病灶残留为0.75±0.18,差异均有统计学意义(均P<0.05),且miRNA-429水平是影响pCR的独立危险因素(HR=9.747,95%CI为1.565~28.849,P=0.044),对无病生存期(P=0.003)及总生存期(P=0.004)均有影响。结论血清中miRNA-429表达水平可作为乳腺癌患者接受TAC方案新辅助化疗后临床疗效的预测指标。

OBJECTIVE Neoadjuvant chemotherapy for breast cancer has different effects.It is hoped that detecting the expression level of miRNA-429 in serum can be used as a neoadjuvant chemotherapy for adriamycin-docetaxel-cyclophosphamide(TAC)in breast cancer patients.METHODS A prospective analysis was performed on 146 breast cancer patients treated in our hospital from January 2012 to January 2016 and receiving TAC neoadjuvant chemotherapy.The levels of miRNA-429 in serum and Ki-67,HER2,estrogen receptor(ER)and progesterone receptor(PR)expression differences before and after neoadjuvant chemotherapy were compared.The effects of miRNA-429 expression on patients with pathologic complete remission(pCR),disease-free survival and overall survival were analyzed.RESULTS According to the differential expression of Ki-67,HER2,ER and PR,146patients with breast cancer were divided into 20cases(14%)Luminal A,52 cases(36%)Luminal B,27 cases(18%)ER^+HER2^+,25 cases(17%)ER^-HER2^-,22cases(15%)ER^-HER2^+.Luminal B(73%),ER^+HER2^+(100%),ER^-HER2^-(72%),and ER^-HER2^+(77%)were higher than Luminal A(30%)in total treatment efficiency.However,there was no significant difference in the pCR rates between the subtypes of breast cancer(U=8.919,P=0.063).There was no significant difference in the serum levels of miRNA-429in all breast cancer subgroups before and after neoadjuvant chemotherapy.According to TAC-NC chemotherapy,the remaining lesions were pCR(3.34±0.47),low lesions(2.58±0.35),moderate lesions(1.28±0.36),severe lesions(0.75±0.18),and difference in relative expression of miR-429 was statistically significant(P<0.05).miRNA-429 levels were independent risk factors for pCR(RR=9.747,95%CI=1.565-28.849,P=0.044),and had significant effects on diseasefree survival and overall survival(P=0.003,P=0.004).CONCLUSIOMN The level of miRNA-429 in serum can be used as a predictor of clinical outcome in patients with breast cancer receiving neoadjuvant TAC.