微小核糖核酸-200b-3p、血管内皮生长因子A在食管鳞状细胞癌组织中的表达及其与复发转移相关性

Expression of microRNA-200b-3p and vascular endothelial growth factor A in esophageal squamous cell carcinoma tissue and their correlation with recurrence and metastasis

目的探讨食管鳞状细胞癌组织中微小核糖核酸-200b-3p(miR-200b-3p)、血管内皮生长因子A(VEGFA)表达及其与复发转移的关系。方法回顾性收集2013年12月至2015年12月于河北省退役军人总医院经手术切除且经组织病理证实的95例食管鳞状细胞癌病人的食管鳞状细胞癌组织及相应的癌旁正常组织。采用实时荧光定量PCR法检测组织中miR-200b3p、VEGFA mRNA表达,采用免疫组化法检测组织中VEGFA表达。采用Pearson检验分析食管鳞状细胞癌病人miR-200b-3p与VEGFA mRNA表达的相关关系;随访5年,采用Kaplan-Meier法分析食管鳞状细胞癌组织中miR-200b-3p、VEGFA表达与病人复发转移的关系,采用Cox比例风险模型分析影响食管鳞状细胞癌病人复发转移的危险因素。结果与癌旁正常组织比较,食管鳞状细胞癌组织中miR-200b-3p表达水平明显降低[(1.00±0.24)比(0.67±0.18),P<0.05],VEGFA mRNA和VEGFA阳性率明显升高[(1.01±0.26)比(1.92±0.50)、(17.89%)比(78.95%),P<0.05]。食管鳞状细胞癌病人miR-200b-3p与VEGFA mRNA表达呈负相关(r=−0.39,P<0.05)。与非复发转移组比较,复发转移组病人食管鳞状细胞癌组织中miR-200b-3p表达水平明显降低[(0.78±0.20)比(0.53±0.14),P<0.05],VEGFA阳性率明显升高[(67.92%)比(92.86%),P<0.05]。食管鳞状细胞癌组织中miR-200b-3p、VEGFA表达与病人组织分化程度、TNM分期有关(P<0.05)。miR-200b-3p低表达者5年复发转移率(55.56%)明显高于高表达者(34.00%)(P<0.05),VEGFA高表达者5年复发转移率(55.17%)明显高于低表达者(27.03%)(P<0.05)。组织分化程度、miR-200b-3p低表达、VEGFA高表达是影响食管鳞状细胞癌病人复发转移的独立危险因素(P<0.05)。结论食管鳞状细胞癌组织中miR-200b-3p表达下调,VEGFA表达上调,二者均可作为评定病人复发转移的临床参考指标。

Objective To investigate the expression of microRNA-200b-3p(miR-200b-3p)and vascular endothelial growth factor A(VEGFA)in esophageal squamous cell carcinoma tissue and their relationship with recurrence and metastasis.Methods Esophageal squamous cell carcinoma tissue and corresponding adjacent normal tissue surgically resected and confirmed by histopathology of 95 patients,who were admitted to Hebei General Hospital for Veterans from December 2013 to December 2015,were collected retrospectively.The expressions of miR-200b-3p and VEGFA mRNA were detected by real-time fluorescence quantitative PCR,and the expression of VEGFA was detected by immunohistochemistry.Pearson test was used to analyze the correlation between miR-200b-3p and VEGFA mRNA expressions in patients with esophageal squamous cell carcinoma.After 5 years of follow-up,Kaplan-Meier method was used to analyze the relationship between the expressions of miR-200b-3p and VEGFA and the recurrence and metastasis of esophageal squamous cell carcinoma;Cox proportional risk model was used to analyze the risk factors of recurrence and metastasis in patients with esophageal squamous cell carcinoma.Results Compared with normal adjacent tissues,miR-200b-3p expression level in esophageal squamous cell carcinoma tissues was significantly decreased[(1.00±0.24)vs.(0.67±0.18);P<0.05],VEGFA mRNA and VEGFA positive rates were significantly increased[(1.01±0.26)vs.(1.92±0.50),17.89%vs.78.95%;P<0.05].There was a negative correlation between miR-200b-3p and VEGFA mRNA expressions in patients of esophageal squamous cell carcinoma(r=−0.39,P<0.05).Compared with non-recurrent metastasis group,the expression level of miR-200b-3p in recurrent metastasis group was significantly decreased[(0.78±0.20)vs.(0.53±0.14);P<0.05],and the positive rate of VEGFA was significantly increased(67.92%vs.92.86%;P<0.05).The expressions of miR-200b-3p and VEGFA in esophageal squamous cell carcinoma tissue was related to the degree of tissue differentiation and TNM staging(P<0.05).The 5-year recurrence and metastasis rateof patients with low expression of miR-200b-3p was significantly higher than that of patients with high expression(55.56%vs.34.00%,P<0.05);the 5-year recurrence and metastasis rate of high expression of VEGFA was significantly higher than that of patients with low expression(55.17%vs.27.03%,P<0.05).Tissue differentiation,low expression of miR-200b-3p and high expression of VEGFA were independent risk factors for recurrence and metastasis of esophageal squamous cell carcinoma(P<0.05).Conclusion The expression of miR-200b-3p was down regulated and the expression of VEGFA was up-regulated in esophageal squamous cell carcinoma tissue,both of which can be used as clinical reference indexes to evaluate the recurrence and metastasis of the disease.