自噬相关基因Beclin1和微管相关蛋白轻链3在胃癌组织中的表达及临床意义

Expression of autophagy-related genes Beclin 1 and microtubule-associated protein 1 light chain 3 in gastric cancer and their clinical significance

目的 检测自噬相关基因Beelin 1和微管相关蛋白轻链3（LC3）在胃癌组织中的表达,探讨其与胃癌临床病理参数及患者预后的关系.方法 应用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶（SP）法分别检测96例胃癌石蜡组织和癌旁组织中Beclin 1和LC3的蛋白表达水平.应用实时定量聚合酶链反应（Real-time PCR）和Western blot检测27例新鲜胃癌组织和相应癌旁组织中mRNA和蛋白的表达.结果 新鲜胃癌组织中Beclin l mRNA（ΔCt：5.90±1.52）及蛋白（1.060±0.112）的表达水平较癌旁组织（ΔCt：7.50±1.22;0.964±0.130）高,两者之间差异有统计学意义（=4.87,t=4.643,P＜0.05）.新鲜胃癌组织中LC3 mRNA（ΔCt：5.00±1.34）及蛋白（1.115±0.111）的表达水平较癌旁组织（ΔCt：6.62±1.51;1.002±0.134）高,两者之间差异有统计学意义（t=5.90,t=5.653,P＜ 0.05）.在胃癌石蜡组织中,Beclin l蛋白和LC3表达阳性率（67.7％、64.6％）均高于癌旁组织（45.8％、40.6％）,差异有统计学意义（P＜0.01）.Beclin 1蛋白和LC3均与肿瘤的分化程度、浸润深度、淋巴结转移以及临床分期有关（P＜0.05）.Beclin 1和LC3蛋白阳性表达患者的5年生存率明显低于阴性表达者（P＜0.01）.结论 Beclin 1和LC3蛋白表达增高与胃癌的发生、发展相关,提示其发挥着癌基因的作用.

Objective To detect the expression of Autophagy-related Genes Beclin 1 and microtubule-associated protein 1 light chain 3 （LC3） protein in gastric cancer and to analyze the correlations with clinical pathological parameters and prognosis of patients with gastric carcinoma.Methods The expression of Beclin 1 and LC3 proteins were examined in 96 paraffin blocks of the gastric cancer and adjacent normal gastric mucosa by Immunohistochemical SP method.The expression levels of mRNA and proteins in 27 fresh gastric carcinoma samples and their corresponding adjacent noncancerous tissues were examined by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blotting.Results The level of Beclin 1 mRNA （ΔCt：5.90 ± 1.52） and Beclin 1 protein （1.060 ±0.112） in fresh gastric carcinoma tissues was significantly higher than that （ΔCt：7.50 ± 1.22; 0.964 ±0.130） in their adjacent normal tissues （t =4.87,t =4.643,P ＜ 0.05）.The level 3 of LC3 mRNA （Δ Ct：5.00 ± 1.34） and LC3 protein （1.115 ±0.111） in fresh gastric carcinoma tissues was significantly higher than that （ΔCt：6.62 ±1.51 ; 1.002 ± 0.134） in their adjacent normal tissues （t =5.90,t =5.653,P ＜ 0.05）.The positive percentage of Beclin 1 proteins and LC3 proteins in paraffin blocks of the gastric cancer was 67.7％ and 64.6％,which was significantly higher than that 45.8％ and 40.6％ in tumor adjacent tissue （P ＜0.01）.Beclin 1 and LC3 protein expressions were correlated with pathological differentiation,invasion depth,lymph node metastasis,tumor stage （P ＜0.05）.There was a significant correlation between Beclin 1 and LC3 protein in gastric cancer （r =0.420,P ＜ 0.01）.The patients with positive expression of Beclin 1 and LC3 proteins had a significantly lower 5-year survival rate than those with negative expression （P ＜ 0.01）.Conclusion Up-regulation of Beclin 1 and LC3 correlate with the genesis and development of gastric carcinoma.