血清miR-191在食管癌复发中的作用及机制研究

Relapse is the major treatment failure of esophageal carcinoma, which belongs to the most frequent malignant diseases. It is an urgent and important clinical issue to forecast as soon as possible the cases with high risk of recurrence and give appropriate treatments. Recent studies have indicated that serum micoRNAs (miRNAs) can be used as biomarkers to predict prognosis such as relapse. Our preliminary experiments shows that: ① A signature consisting of 10 serum miRNAs discriminates recrudesent esophageal carcinoma patients from non-relapse ones , ② miR-191 expression was significantly increased in serum of esophageal carcinoma patients with relapse；high expression of serum miR-191 suggest poor prognosis, ③The growth and proliferation of esophageal cancer cells was significantly inhibited after transiently transfected with miR-191 inhibitor. But the mechanism is unclear. In this study, we will detect serum miRNA expression of 400 esophageal cancer patients with clinical data and follow-up information by reverse transcription-polymerase chain reaction (qRT-PCR) to clarify the prediction role of serum miR-191 on relapse and prognosis of esophageal cancer, and to provide guidance for individualized treatment of esophageal cancer. Furthermore, we will do experimental studies in vitro and in vivo to elucidate the role of miR-191 in growth and proliferation of esophageal cancer and its mechanism, to provide new targets for individualized treatment of esophageal cancer.

食管癌是我国最常见的恶性肿瘤之一。复发是食管癌治疗失败的主要模式，寻找分子指标来预测高复发风险病例并给予恰当治疗是临床急需解决的重要问题。近年研究发现血清microRNA可作为预测肿瘤复发等预后的分子指标。我们的预实验结果显示：①由10个血清microRNA组成的分子标签能够准确区分复发和无复发的食管癌，②血清miR-191在复发食管癌血清中明显升高；miR-191高表达时复发率高，预后差，③瞬转miR-191的inhibitor可抑制食管癌细胞株的生长增殖，但其机制不详。本申请项目在此基础上，拟采用定量PCR方法检测400例临床信息及随访完整的食管癌患者血清样本，进一步明确血清miR-191在预测食管癌复发中的作用，为食管癌“个体化”治疗提供指导；并进一步通过体外、体内实验阐明miR-191在食管癌复发中的作用及机制，从而为食管癌治疗提供新靶点奠定基础。