幽门螺杆菌相关胃癌发生不同阶段miRNAs表达与临床研究

目的 观察幽门螺杆菌（Helicobacter pylori, H. pylori）感染的慢性非萎缩性胃炎（no-atrophic gastritis，NAG）→萎缩性胃炎（chronic atrophic gastritis，CAG）→肠上皮化生（intestinal metaplasia，IM）→非典型增生（dysplasia，DYS）→胃癌（gastric cancer，GC）五个不同阶段miR-1、miR-20a、miR-34a、miR-423-5p表达变化规律及其与临床的关系。方法 收集胃镜及病理证实的上述胃癌发生五个不同阶段且H. pylori感染的患者（依次为44、47、43、50、45例），胃癌无H. pylori感染者46例，胃黏膜正常（normal gastric mucose，NGM）63例的血清标本，采用Real-time PCR法检测无H. pylori感染者miR-1、miR-20a、miR-34a、miR-423-5p表达。结果 H. pylori感染NAG→GC不同阶段，miR-1、miR-20a、miR-34a、miR-423-5p表达逐渐升高（P<0.05），GC阶段最高，miR-1、miR-20a CAG→GC阶段均高于NGM（P<0.05），与NGM比较差异有统计学意义（P<0.05）；其表达程度与GC发生阶段呈正相关（P<0.001）；GC组H. pylori感染者较无H. pylori感染者miR-1、miR-20a、miR-34a、miR-423-5p表达升高（P<0.05）。结论 H. pylori感染CAG→GC阶段miR-1、miR-20a、miR-34a、miR-423-5p表达升高，向胃癌演进中呈逐渐升高趋势，miR-1、miR-20a、miR-34a、miR-423-5p高表达可能是H. pylori感染后导致胃癌发生发展的重要机制，miR-1、miR-20a、miR-34a可作为诊断早期胃癌的标记物。

MiRNAs expression in different stages of Helicobacter pylori associated gastric cancer and clinical study

Abstract: Objective To explore the relationship between the expressions of miR-1, miR-20a, miR-34a and miR-423-5p and clinical manifestations in the sequential pathological stages of Helicobacter pylori (H. pylori) associated no-atrophic gastritis (NAG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM), dysplasia (DYS) and gastric cancer (GC). Methods According to the results of gastroscope and pathological analysis, the serum specimens of gastric cancer patients with H. pylori infection (including 44 cases in NAG stage, 47 cases in CAG stage, 43 cases in IM stage, 50 cases in DYS stage and 45 cases in GC stage), those without H. pylori infection (GC, n=46) and those with normal gastric mucosa without H. pylori infection (NGM, n=63) were collected. The expressions of miR-1, miR-20a, miR-34a and miR-423-5p were detected by using real-time PCR. Results The expressions of miR-1, miR-20a, miR-34a and miR-423-5p increased gradually from NAG stage to GC stage in patients with H.pylori infection (P<0.05), reaching the highest point in GC stage. The expressions of miR-1 and miR-20a in stages from CAG to GC were significantly higher than in NGM group (P<0.05). The expressions of miR-1, miR-20a, miR-34a and miR-423-5p were positively correlated with the developmental stages of GC (P<0.001), which were higher in GC patients with H. pylori infection than in those without (P<0.05). Conclusion The expressions of miR-1, miR-20a, miR-34a and miR-423-5p increased gradually from CAG stage to GC stage, which might be an important mechanism of to the development of gastric cancer. The miR-1, miR-20a and miR-34a can be used as the markers for the diagnosis of early gastric cancer.