食管癌病人血清中miR-33a-5p和SIRT6表达及其与临床病理特征的关系

Expression of miR-33a-5p and SIRT6 in the serum of esophageal cancer patients and their relationship with clinical pathological characteristics

目的探讨食管癌病人血清微小RNA-33a-5p(miR-33a-5p)、沉默信号调节蛋白6(Sirtuin6,SIRT6)表达水平及其与临床病理特征、预后的关系。方法2018年3月~2020年3月期间收治的食管癌初诊病人123例(食管癌组),食管炎病人94例(良性病变组),同期体检健康者72例(对照组);收集食管癌病人临床病理资料。采用实时荧光定量PCR法检测三组血清中miR-33a-5p、SIRT6 mRNA的表达情况,分析食管癌病人血清miR-33a-5p、SIRT6 mRNA表达水平与临床病理特征的关系;TargetScanHuman网站预测miR-33a-5p与SIRT6的靶向关系;Pearson法分析食管癌病人血清miR-33a-5p与SIRT6 mRNA表达水平相关性;采用Kaplan-Meier法分析食管癌病人血清miR-33a-5p、SIRT6 mRNA表达水平与病人预后的关系;Cox回归分析食管癌病人预后的影响因素。结果食管癌组血清miR-33a-5p表达水平高于良性病变组、对照组,差异有统计学意义(P<0.05),血清SIRT6 mRNA表达水平低于良性病变组、对照组,差异有统计学意义(P<0.05);TargetScanHuman网站预测miR-33a-5p与SIRT6存在靶向结合位点,食管癌病人血清miR-33a-5p与SIRT6 mRNA表达水平呈负相关关系(r=-0.468,P<0.05);食管癌病人血清miR-33a-5p、SIRT6 mRNA表达水平与TNM分期、淋巴结转移、分化程度有关;血清miR-33a-5p低表达与SIRT6 mRNA高表达食管癌病人3年生存率明显高于miR-33a-5p高表达与SIRT6 mRNA低表达食管癌病人,差异有统计学意义(P<0.05);Cox回归分析结果显示,miR-33a-5p高表达及SIRT6 mRNA低表达是食管癌病人死亡的独立危险因素(P<0.05)。结论食管癌病人血清miR-33a-5p表达水平升高,SIRT6 mRNA表达水平降低;二者表达水平与食管癌病人临床病理特征和病人预后相关。

Objective To investigate the expression levels of serum microRNA-33a-5p(miR-33a-5p)and Sirtuin6(SIRT6)in patients with esophageal cancer,and their relationship with clinical pathological characteristics and prognosis.Methods From March 2018 to March 2020,123 newly diagnosed patients with esophageal cancer(esophageal cancer group)and 94 patients with esophagitis(benign lesion group)admitted to our hospital were collected as the research subjects,another 72 healthy individuals who underwent physical examination were regarded as the health control group;the clinical and pathological characteristics of esophageal cancer patients were collected.Real-time fluorescence quantitative PCR method was applied to detect the expression of miR-33a-5p and SIRT6 mRNA in three groups of serum,the relationship between the expression levels of serum miR-33a-5p and SIRT6 mRNA in esophageal cancer patients and clinical pathological characteristics was analyzed;TargetScanHuman website was applied to predict the targeting relationship between miR-33a-5p and SIRT6;Pearson method was applied to analyze the correlation between serum miR-33a-5p and SIRT6 mRNA expression levels in esophageal cancer patients;Kaplan-Meier method was applied to analyze the relationship between the expression levels of serum miR-33a-5p and SIRT6 mRNA in esophageal cancer patients and their prognosis;Cox regression was applied to analyze the prognostic factors of esophageal cancer patients.Results The expression level of serum miR-33a-5p in the esophageal cancer group was greatly higher than that in the benign lesion group and healthy control group(P<0.05),the expression level of serum SIRT6 mRNA was greatly lower than that of the benign lesion group and healthy control group(P<0.05);TargetScanHuman website predicts that there was a targeted binding site between miR-33a-5p and SIRT6,and there was a negative correlation between serum miR-33a-5p and SIRT6 mRNA expression levels in esophageal cancer patients(r=-0.468,P<0.05);the expression levels of serum miR-33a-5p and SIRT6 mRNA in esophageal cancer patients were related to TNM staging,lymph node metastasis,and degree of differentiation;the 3-year survival rate of esophageal cancer patients with low expression of serum miR-33a-5p and high expression of SIRT6 mRNA was greatly higher than that of esophageal cancer patients with high expression of miR-33a-5p and low expression of SIRT6 mRNA(P<0.05);Cox regression analysis showed that high expression of miR-33a-5p and low expression of SIRT6 mRNA were independent risk factors for death in esophageal cancer patients(P<0.05).Conclusion The expression level of serum miR-33a-5p in esophageal cancer patients is greatly increased,while the expression level of SIRT6 mRNA is greatly reduced;the expression levels of both are closely related to the clinical pathological characteristics and prognosis of esophageal cancer patients.