早期胃癌中miR-17表达与内镜黏膜下剥离术预后的关系及其靶向PTEN的初步验证

The relationship between the expression of miR-17 and the prognosis of endoscopic submucosal dissection in early gastric cancer and the preliminary verification of its target on PTEN

目的研究早期胃癌中miR-17表达与内镜黏膜下剥离术预后的关系并初步验证miR-17对第十号染色体缺失与磷酸酶和张力蛋白同源基因(PTEN)的靶向作用。方法选择2015年1月至2017年12月期间接受内镜黏膜下剥离术的早期胃癌患者及同期经病理证实为正常胃黏膜的患者,检测miR-17、PTEN的表达量;随访早期胃癌患者的复发情况,COX模型分析复发的影响因素,ROC曲线分析miR-17预测复发的价值。结果早期胃癌组织中miR-17的表达水平明显高于正常胃黏膜组织且T1b期、低未分化早期胃癌组织中miR-17的表达水平明显高于T1a期、中高分化早期胃癌组织;T1b、miR-17表达增多是早期胃癌患者术后复发的危险因素;miR-17预测早期胃癌术后复发的最佳截点为0.6850;早期胃癌组织中PTEN的表达水平明显低于正常胃黏膜组织且与miR-17表达水平呈负相关,miR-17靶向结合PTEN基因mRNA 3’UTR的第272-278碱基。结论miR-17表达增加是早期胃癌患者内镜黏膜下剥离术后复发的危险因素,对术后复发具有预测价值,靶向抑癌基因PTEN是其可能的生物学作用。

Objective To study the relationship between the expression of miR-17 and the prognosis of endoscopic submucosal dissection in early gastric cancer and to verify the targeting effect of miR-17 on gene of phosphate and tension homology deleted on chromsome ten(PTEN).Methods Patientswith early gastric cancer who underwent endoscopic submucosal dissection in our hospital from January 2015 to December 2017 and patients with normal gastric mucosa confirmed by pathology at the same time were selected.The expression of miR-17 and PTEN were measured.The recurrence of early gastric cancer was followed up.Cox model was used to analyze the influencing factors of recurrence and ROC curve was used to analyze the value of miR-17 in predicting recurrence.Results The expression level of miR-17 in early gastric cancer was significantly higher than that in normal gastric mucosa,and the expression level of miR-17 in T2 stage,low undifferentiated and submucosal early gastric cancer were significantly higher than those in T1 stage,middle and high differentiated and intramucosal early gastric cancer.Submucosal infiltration and increased expression of miR-17 were risk factors for postoperative recurrence of early gastric cancer.The best cutoff of miR-17 for predicting postoperative recurrence of early gastric cancer was 0.6850.The expression level of PTEN in early gastric cancer was significantly lower than that in normal gastric mucosa and negatively correlated with the expression level of miR-17.miR-17 targeted bind to the 272-278 base of PTEN gene mRNA 3’UTR.Conclusion The increased expression of miR-17 is a risk factor for the recurrence of early gastric cancer patients after endoscopic submucosal dissection,and it has a predictive value for the recurrence.Targeting tumor suppressor gene PTEN is its possible biological role.