复发转移性乳腺癌患者血浆miRNA表达水平与临床病理特征、化疗疗效及预后关系的研究

摘要

目的：探讨血浆中miR-16、miR-34a、miR-200a、miR-375、miR-451化疗前、后表达水平的变化与乳腺癌临床病理特征、化疗疗效及预后之间的关系。方法选取复发转移性乳腺癌患者79例，采用GenEx ver-sion6软件、Normfinder软件和Genorm软件确定本实验的内对照，采用实时荧光定量PCR法检测患者化疗前及化疗2个周期时的血浆miRNA表达水平，并分析化疗前、后表达水平与患者临床病理特征、化疗疗效及预后的关系。结果 miR-34a为相对表达最稳定的内对照。血浆miR-451高表达的患者激素受体（hormone receptor， HR）阳性率显著高于低表达者（P=0.031），分别为84.2%和62.5%。血浆miR-200a化疗后表达变化与客观缓解率（objective response rate，ORR）显著相关（P=0.032），miR-200a化疗后表达升高者的ORR显著高于降低者，分别为57.9%和29.3%。血浆miR-200a化疗后表达水平升高组的无进展生存时间（progression-free survival，PFS）与降低组相比，组间差异具有统计学意义（P=0.009），分别为10.3个月和5.2个月。miR-16、miR-200a、miR-375和miR-451表达水平及化疗后变化对总生存时间（overall survival，OS）均无显著影响。结论血浆miRNA化疗前、后表达水平对复发转移性乳腺癌患者临床病理特征、化疗疗效及预后有一定的预测价值。%Objective To explore the feasibility and value of plasma miRNA as a biomarker for clinicopathologi-cal characteristics and chemosensitivity in metastatic breast cancer patients. Method 79 patients with metastatic breast cancer were enrolled. The expression levels of circulating plasma miR-16, miR-34a, miR-200a, miR-375, and miR-451 were assessed by qRT-PCR method. The correlation between miRNAs expression levels and clinical patho-logical features, chemosensitivity and prognosis were analyzed. Result miR-451 expression level was significantly associated with estrogen receptor or hormone receptorstatus (P<0.05). The change of plasma miR-200a before and af-ter cheomtherpy was significantly associated with objective response rate (ORR). Plasma miR-200a level before che-motherapy and its change after chemotherapy significantly affected the progression free survival (PFS) of the patients. Conclusion The change of plasma miR-200a before and after cheomtherpy might be a predictive biomarker for che-mosensitivity and PFS in patients with metastatic breast cancer.