microRNA-101和环氧合酶-2在胃癌中的表达及其临床意义

Expressions and Clinical Significance of microRNA-101 and Cyclooxygenase-2 in Gastric Cancer

背景:microRNAs是一类对靶基因表达具有转录后调控作用的非编码小RNA。microRNA-101(miR-101)在多种恶性肿瘤中呈低表达,而过表达外源性miR-101可发挥肿瘤抑制作用。前期体内、外实验发现外源性miR-101可抑制胃癌细胞增殖和环氧合酶-2(COX-2)表达。目的:检测胃癌组织中的miR-101、COX-2表达并探讨其临床意义。方法:收集手术切除胃癌组织和配对癌旁非癌组织标本30例,以实时荧光定量RT-PCR检测miR-101、COX-2mRNA表达,分析两者间以及两者与胃癌主要临床病理特征的关系。结果:绝大多数胃癌组织中miR-101表达低下,COX-2 mRNA则呈过表达。胃癌组织与癌旁非癌组织间miR-101、COX-2 mRNA表达量差异显著(P<0.01),且两者表达在癌组织和癌旁组织中均呈负相关(癌组织:r=-0.767,P=0.000;癌旁组织:r=-0.718,P=0.000)。TNMⅢ、Ⅳ期胃癌和伴淋巴结转移的胃癌中,miR-101表达分别显著低于TNMⅠ、Ⅱ期病例和无淋巴结转移病例(P<0.05),COX-2 mRNA表达分别显著高于TNMⅠ、Ⅱ期病例和无淋巴结转移病例(P<0.05)。结论:miR-101与COX-2之间的负相关性可能有助于胃癌的临床诊断;miR-101表达低下伴COX-2过表达与胃癌临床进展和转移有关,对预后判断有一定参考价值。

Background： MicroRNAs are a class of small non-coding RNAs that regulate target gene expression posttranscriptionally. Down-regulated expression of microRNA-101 （ miR-lO1 ） has been found in a variety of cancers, while ectopic expression of miR-101 exerts tumor suppressive effect. Previous study revealed that exogenous miR-101 inhibited cell proliferation and decreased cyclooxygenase-2 （ COX-2 ） expression in gastric cancer cells both in vivo and in vitro. Aims ： To investigate the expressions and clinical significance of miR-101 and COX-2 in gastric cancer. Methods： A total of 30 reseeted gastric cancer specimens and paired adjacent non-cancerous tissues were collected for assessment of miR-101 and COX-2 mRNA expressions by real-time quantitative RT-PCR. Correlation between miR-101 and COX-2, as well as their correlations with the major elinicopathological characteristics of gastric cancer were analyzed. Results： Expression of miR-101 was down-regulated and COX-2 mRNA was overexpressed in most gastric cancer tissues. Significant differences were seen in expression levels of miR-101 and COX-2 mRNA between cancerous and adjacent non-cancerous tissues （P 〈0.01 ）. miR- 101 expression was negatively correlated with COX-2 mRNA expression in both cancerous （r = -0. 767, P = 0. 000 ） and adjacent tissues （r = -0. 718, P = 0. 000）. Furthermore, miR-101 expression was significantly lower in gastric cancers with TNM stage 11I and IV than those with TNM stage Ⅰ and Ⅱ （ P 〈 0.05 ） , as well as in gastric cancers with lymph node metastasis than those without lymph node metastasis （P 〈 0.05 ） ; while COX-2 mRNA expression was significantly higher in TNM stage Ⅲ and Ⅳ and lymph node metastatic gastric cancers （P 〈 0.05 ）. Conclusions ： Inverse correlation between miR-101 and COX-2 is a promising biomarker for the diagnosis of gastric cancer. Down-regulated miR-101 expression and parallel COX-2 overexpression is correlated with the clinical progression and metastasis of gastric cancer, and might be a potential predictor for prognosis.