长链非编码RNA TUG1在胃癌患者中的表达及其对预后的影响

摘要

Background:The incidence of gastric cancer is gradually rising in recent years,long non-coding RNA taurine up-regulated gene 1 (TUG1)may have certain effects on the occurrence and progression of gastric cancer. Aims:To study the expression TUG1 in gastric cancer tissue and its effect on prognosis of patients with gastric cancer,and study the correlation between TUG1 and p27,cyclin D1. Methods:Surgically resected gastric cancer tissues and corresponding distal normal tissues of 48 gastric cancer patients from June 2013 to December 2013 at Qingdao Municipal Hospital were collected. qRT-PCR was used to detect the mRNA expression of TUG1,and its relationship with clinicopathological features was analyzed. Protein expressions of p27 and cyclin D1 were determined by Western blotting,and correlation with expression of TUG1 was analyzed. Kaplan-Meier was used to analyze the relationship between expression of TUG1 and prognosis. Results:The mRNA expression of TUG1 in gastric cancer tissues was significantly higher than that in corresponding normal tissues (6. 18 ± 0. 19 vs. 5. 09 ± 0. 16,P < 0. 05),and was not correlated with gender,age,tumor size,but correlated with lymph node metastasis,tumor differentiation and TNM staging (P < 0. 01). The protein expression of p27 was significantly decreased in gastric cancer tissues than in normal tissues (0. 1709 ± 0. 0212 vs. 0. 3087 ± 0. 0252,P < 0. 01),while protein expression of cyclin D1 was significantly increased (0. 3417 ± 0. 0271 vs. 0. 2417 ± 0. 0173,P < 0. 01),and the expression of p27 was negatively correlated with expression of cyclin D1 in gastric cancer tissues (r = - 0. 897,P < 0. 01). The expression of TUG1 was negatively correlated with expression of p27 (r = - 0. 730,P < 0. 01),and was positively correlated with expression of cyclin D1 (r = 0. 809,P < 0. 01)in gastric cancer tissues. The median survival time was shorter in gastric cancer patients with high-expressed TUG1 than in patients with low-expressed TUG1 (P < 0. 05). Conclusions:Long non-coding RNA TUG1 plays a role of cancer gene in the development of gastric cancer through p27 /cyclin D1 pathway. Detection of expression of TUG1 has important significance on the prediction of prognosis of gastric cancer patients.%背景:近年胃癌的发生率呈逐步上升的趋势,长链非编码RNA牛磺酸上调基因1(TUG1)对胃癌的发生、发展可能起有一定的作用.目的:研究TUG1在胃癌组织中的表达及其对预后的影响,并进一步探讨TUG1与p27蛋白、细胞周期蛋白D1(cyclin D1)的相关性.方法:收集2013年6月—2013年12月青岛市市立医院48例手术切除的胃癌组织及其相应远端正常组织,采用qRT-PCR法检测TUG1 mRNA表达,并分析其与临床病理特征的关系.采用蛋白质印迹法检测p27、cyclin D1蛋白表达,并分析其与TUG1表达的相关性.采用Kaplan-Meier法分析TUG1表达与预后的关系.结果:胃癌组织中TUG1 mRNA表达显著高于相应正常组织(6.18±0.19对5.09±0.16,P<0.05),且其表达与性别、年龄、肿瘤大小无关,与淋巴结转移、肿瘤分化程度和TNM分期有关(P<0.01).胃癌组织中p27蛋白表达显著低于正常组织(0.1709±0.0212对0.3087±0.0252,P<0.01),cyclin D1蛋白表达显著升高(0.3417±0.0271对0.2417±0.0173,P<0.01),且p27蛋白表达与cyclin D1蛋白表达呈负相关(r=-0.897,P<0.01).胃癌组织中TUG1表达与p27表达呈负相关(r=-0.730,P<0.01),与cyclin D1表达呈正相关(r=0.809,P<0.01).TUG1高表达的胃癌患者生存时间明显低于TUG1低表达者(P<0.05).结论:长链非编码RNA TUG1可能通过p27/cyclin D1途径在胃癌的发生、发展中起癌基因的作用,通过检测TUG1表达对判断胃癌患者预后具有潜在的价值.