中文摘要
Ⅰ型胃神经内分泌肿瘤是一种罕见恶性肿瘤,其恶性程度相对较低,但复发率高,目前预防复发的方法或价格高昂,或创伤较大,患者多难以接受。我们在临床研究中发现,该病患者以肝郁脾虚为主要证型,申请人自拟疏肝健脾方药“疏木六君子汤”可有效降低该病复发率,延长中位复发时间,但其作用机制尚不明确。预实验发现,该病的肿瘤组织和无复发的胃黏膜组织相比,存在miRNA-202-3p异常上调,预测其主要靶基因可能为DUSP1、ATP6V0A2。本项目拟进行多中心前瞻性临床研究,对比中药组和对照组患者胃镜活检组织中miRNA-202-3p及其靶基因的表达差异。同时,构建miRNA-202-3p过表达的神经内分泌细胞,通过双荧光素酶实验进一步验证其靶基因,并观察中药含药血清对其miRNA表达和基因表达的影响,以揭示中药预防该病复发的分子机制。本研究将为临床使用中药预防Ⅰ型胃神经内分泌肿瘤复发提供理论基础和实验依据。
英文摘要
Type I gastric neuroendocrine tumor is a kind of rare neoplasm with relative low malignant and high rate of recurrence. Currently, few prevention methods for its recurrence are acceptable because of high price or trauma. The applicant found in the clinical research that most patients with type 1 gastric neuroendocrine tumor had depressed liver and deficient spleen symptoms, and Shumu Liujunzi Decoction, an experienced formula with Shugan Jianpi Method, can effectively decrease its recurrence and delay median relapse time. However, the specific mechanism was not clear. Our pre-studies observed that abnormal upregulation of miRNA-202-3p existed in gastric tumor tissues but not in gastric mucosa without recurrent, which may be related with targeted genes DUSP1, ATP6V0A2, and so on. This program aims to conduct multi-site, progressive study to compared differences of miRNA-202-3P, DUSP1, ATP6V0A2 expression in patients’ gastric endoscopic biopsies between Traditional Chinese Medicine group and control group. For further exploration of molecular mechanisms how this tumor recurrence prevented by Traditional Chinese Medicine, neuroendocrine cells with miRNA-202-3p overexpression will be constructed to test its targeted genes by dual luciferase experiments, and to test miRNA expressions and gene expressions whether would be affected by serum with Traditional Chinese Medicine. This study will provide theoretical basis and experiment evidence for clinical application of Traditional Chinese Medicine to prevent type I gastric neuroendocrine tumor recurrence.
