长链非编码RNAs MEG3和GAS5在胃癌组织中的表达及其与预后的关系

Expressions of long no-coding RNAs MEG3,GAS5 in gastric cancer tissues and their association with prognosis of gastric cancer patients

目的研究长链非编码RNAs(lncRNAs)母系表达基因3(MEG3)、生长特异抑制物5(GAS5)在胃癌组织中的表达及其与预后的关系,并进一步探讨MEG3与凋亡相关蛋白P53、MDM2的相关性。方法收集2012年9月至2013年6月手术治疗的胃癌切除标本(包括癌组织及对应的远端正常组织)55例,采用实时定量聚合酶链反应qRT-PCR检测胃癌组织中MEG3、GAS5的表达水平(以2-△△ct表示基因相对表达量),并分析其与临床病理参数的关系;Western blot法检测胃癌中P53、MDM2蛋白的相对表达水平,并分析其与MEG3的相关性。结果 (1)MEG3在胃癌组织的相对表达水平(7.98±0.19)低于正常组织(9.47±0.18,P<0.01)。GAS5在胃癌组织的相对表达水平(4.03±0.18)低于正常组织(6.06±0.18,P<0.01)。MEG3、GAS5相对表达水平与年龄、性别、肿瘤大小无相关性,与分化程度、是否淋巴结转移、TNM分期有关(P<0.05,P<0.01)。(2)P53蛋白在胃癌组织中的相对表达水平(0.185 5±0.014 7)低于正常组织(0.258 7±0.018 5),MDM2蛋白在胃癌组织中的相对表达水平(0.295 1±0.016 8)高于正常组织(0.195 5±0.015 1),差异均有统计学意义(P均<0.01)。(3)癌组织中MEG3的表达水平与P53蛋白水平呈正相关(r=0.591,P<0.01),而与MDM2蛋白水平呈负相关(r=-0.346,P<0.05)。(4)MEG3、GAS5高表达者较低表达者中位生存期明显延长(P均<0.01)。结论 MEG3、GAS5基因在胃癌发生发展过程中起抑癌基因的作用,MEG3可通过p53途径发挥抑癌作用。检测MEG3、GAS5基因的表达水平对判断胃癌预后有一定价值。

Objective To investigate the expressions of long non-coding RNAs （lncRNAs） materally expressed gene 3 （MEG3） and growth arrest-specific 5 （GAS5）in gastric cancer tissues and their relationships with the prognosis and ex- plore the associations of MEG3 with apoptosis-related proteins P53 and MDM2 further. Methods The specimens of surgi- cal resection from 55 gastric cancer patients including cancer tissues and corresponding distal normal tissues between September 2012 and June 2013 were collected. The real-time fluorescence quantitative polymerase chain reaction （qRT-PCR） was used to detect the relative expression levels of MEG3 and GAS5 （ represented by 2^-△△Ct）, and the associations of their expression levels with clinical pathological parameters were analyzed. Western blot method was used to detect relative expression levels of P53 and MDM2 proteins, and the correlations of their expression levels with MEG3 were analyzed. Results The relative expression levels of MEG3 and GAS5 in gastric cancer tissues were all significantly lower than those in normal tissues [ （7.98± 0.19 ） vs （9.47 ±0.18 ） , （4.03±0.18 ） vs （ 6.06 ＋_ 0.18 ） , all P 〈 0.01 ]. The relative expression levels of MEG3 and GAS5 were not correlated with age, sex, tumor size but were significantly correlated with tumor＇ differ- entiation degree, lymph node metastasis, TNM staging （ P 〈 0.05, P 〈 0. 01 ）. The relative expression level of P53 protein in gastric cancer tissues was significantly lower than that in normal tissues [ （0. 185 5 ±0. 014 7） vs （0. 258 7 ±0.018 5 ） , P 〈 O. 01 ] , and the relative expression level of MDM2 protein in gastric cancer tissues was significantly higher than that in normal tissues [ （0.295 1±0. 016 8）vs（0. 195 5 ±0. 015 1 ） ,P 〈0.01 ]. The expression level of MEG3 in cancer tissues was positively correlated with P53 protein （r = 0.591 ,P 〈 0.01 ）, but the expression level of MEG3 was negatively correla- ted with MDM2 protein（ r = - 0.346 ,P 〈 0.05 ）. The median survival times in patients with high-expressions of MEG3 and GAS5 were significantly prolonged compared with the patients with low-expressions of MEG3 and GAS5 （ all P 〈 0.01 ）. Conclusions MEG3 and GAS5 gene play the role of anti-oncogene in the occurring and development process of gastric cancer, and the effect of cancer-inhibition of MEG3 may be through p53 pathway. Detecting the expression levels of MEG3 and GAS5 gene has a certain value for judging the prognosis of gastric cancer.