胰腺癌患者及大鼠血清中microRNA-21和microRNA-155的表达及其意义

The expression levels and significance of serum microRNA-21 and microRNA-155 from patients and rats with pancreatic cancer

目的探索胰腺癌患者和胰腺癌大鼠血清中microRNA(miRNA)-21和miRNA-155的表达水平及其用于胰腺癌诊断的价值。方法前瞻性收集2016年1月至2016年12月期间福建医科大学附属协和医院收治的18例胰腺癌患者(胰腺癌组)及同期收治的12例胰腺良性疾病(胰腺良性疾病组)患者的临床资料和血清样本,采用实时荧光定量法检测血清中miRNA-21和miRNA-155的表达水平。同时建立20只由7, 12-二甲基苯并蒽(DMBA)诱导的胰腺癌大鼠模型,并设置对照(10只空白对照组大鼠行假手术),采集胰腺癌大鼠组(建模成功的胰腺癌大鼠)和空白对照组大鼠的血清,同法检测血清中miRNA-21和miRNA-155的表达水平。结果胰腺癌组患者血清中miRNA-21和miRNA-155的中位表达水平分别为1.99(1.43～5.30)和7.06(4.98～21.48),胰腺良性疾病组患者分别为1.28(0.58～2.01)和2.20(1.76～3.02),胰腺癌组患者的血清miRNA-21和miRNA-155表达水平均较高(Z=–2.621,P=0.009;Z=–3.430,P=0.001)。动物实验中,实验组建模成功并存活大鼠11只,空白对照组存活大鼠9只。胰腺癌大鼠组血清中miRNA-21和miRNA-155的中位表达水平分别为2.12(1.33～2.72)和16.45(7.18～25.40),空白对照组大鼠分别为1.00(0.45～1.60)和1.49(1.25～1.97),胰腺癌大鼠组血清中mi RNA-21和miRNA-155的表达水平均较高(Z=–2.621,P=0.009;Z=–3.609,P<0.001)。在区分胰腺癌和胰腺良性疾病方面,血清miRNA-21表达水平的最佳临界值为4.21,此时其灵敏度和特异度分别为75.0%和61.1%;血清miRNA-155表达水平的最佳临界值为4.67,此时其灵敏度和特异度均为83.3%。结论胰腺癌患者及大鼠血清中miRNA-21和miRNA-155的表达水平均异常升高,血清miRNA-155水平在一定程度上有助于区分胰腺癌与胰腺良性疾病。

Objectives To evaluate the expression levels of serum microRNA-21（miRNA-21） and microRNA-155（miRNA-155） from patients and rats with pancreatic cancer, and to explore its value in the diagnosis of pancreatic cancer. Methods The clinical materials and the serum samples from 18 patients with pancreatic cancer（pancreatic cancer group） and 12 patients with benign pancreatic disease（benign pancreatic disease group） admitted to Fujian Medical University Union Hospital between January 2016 and December 2016 were collected prospectively. The real-time fluorescent quantitative PCR was performed to detect the levels of serum miRNA-21 and miRNA-155. 7, 12-dimethylbenz（a） anthracene（DMBA）-induced pancreatic cancer rat models（n=20） and the models of the blank control group（sham operation, n=10） were established and the serum samples from the pancreatic cancer group and the blank control group were measured by the real-time fluorescent quantitative PCR, to detect the levels of miRNA-21 and miRNA-155. Results The median expression levels of serum miRNA-21 and miRNA-155 were 1.99（1.43–5.30） and 7.06（4.98–21.48） in the pancreatic cancer group, as well as 1.28（0.58–2.01） and 2.20（1.76–3.02） in the benign pancreatic disease group. The expression levels of serum miRNA-21 and miRNA-155 were significantly higher in the pancreatic cancer group（Z=–2.621, P=0.009; Z=–3.430, P=0.001）. In animal studies, the rat models of pancreatic cancer were successfully established and 11 rats with pancreatic cancer were acquired, as well as 9 rats in the blank control group were acquired.The median expression levels of serum miRNA-21 and miRNA-155 were 2.12（1.33–2.72） and 16.45（7.18–25.40） in the rat pancreatic cancer group, as well as 1.00（0.45–1.60） and 1.49（1.25–1.97） in the blank control group. The expression levels of serum miRNA-21 and miRNA-155 were significantly higher in the rat pancreatic cancer group（Z=–2.621,P=0.009; Z=–3.609, P〈0.001）. For distinguishing pancreatic cancer from benign diseases, the best cutoff value of serum miRNA-21 level was 4.21 and the sensitivity and specificity were 75.0% and 61.1% respectively; the best cutoff value of serum miRNA-155 level was 4.67 and the sensitivity and specificity both were 83.3%. Conclusions The serum miRNA-21 and miRNA-155 levels are elevated both in patients and rats with pancreatic cancer. Detection of serum miRNA-155 will be helpful to some extent to distinguish pancreatic cancer from benign diseases.