索拉非尼对肝癌患者血清中肿瘤相关miRNAs的影响

Altered expression levels of miRNAs in serum of patients with hepatocellular carcinoma in the treatment of Sorafenib

目的 探讨索拉非尼治疗前后对肝癌患者血清中肿瘤相关miRNA表达谱改变情况.方法 收集2011年10月～2012年9月在绍兴第二医院及浙江大学医学院附属第一医院接受治疗的6例肝癌患者的血清样本,采用miRNA表达谱芯片检测HCC患者经索拉非尼治疗前后血清中差异表达的miRNAs,并应用实时荧光定量PCR（RT-PCR）对筛选出的miRNAs进行验证.结果 索拉非尼治疗前后肝癌患者血清miRNA表达谱出现明显改变,16个miRNAs在索拉非尼治疗后肝癌患者血清中表达明显升高,10个miRNAs在索拉非尼治疗后肝癌患者血清中表达明显降低.治疗前肝癌患者血清miR-122相对表达值为（1.07±0.32）,治疗1个月后的miR-122相对表达值为（9.10±1.89）,差异有统计学意义（P＜0.05）,较治疗前表达水平显著上调.结论 索拉非尼治疗前后肝癌患者血清中表达谱发生明显变化,索拉非尼对肝癌相关miRNAs的调控可能是其治疗肿瘤的重要机制之一.

Objective To investigate the differential expression of miRNAs in serum of patients with hepatocellular carcinoma （HCC） in the treatment of Sorafenib.Methods Blood samples in 6 patients with HCC in Shaoxing Second Hospital and the First Affiliated Hospital,College of Medicine,Zhejiang University from October 2011 to September 2012 were selected.The miRNA microarray was chosen to assess the level and composition of miRNAs in serum of patients with HCC in the treatment of Sorafenib.Reverse transcription polymerase chain reaction （RT-PCR） was used to validate the data of miRNA microarray.Results There were significant changes in some miRNAs in serum of patients with HCC post Sorafenib treatment （10 miRNAs were more than 2-fold down-regulated and 16 miRNAs were more than 2-fold up-regulated）.Relative expression values of miR-122 before the treatment was （1.07±0.32）,the expression values of miR-122 1 month after the treatment was （9.10±1.89）,the difference was statistically significant （P ＜ 0.05）.Conclusion Sorafenib treatment can make significant changes in the spectra and levels of serum miRNAs in patients with HCC,the regulation of HCC related miRNAs by Sorafenib may be one important mechanism of treatment of cancer.