食管癌组织miR-122-5p、CREB1 mRNA表达变化及其临床意义

Expression changes of miR-122-5p and CREB1 mRNA in esophageal carcinoma and their clinical significance

目的观察食管癌组织微小RNA-122-5p(miR-122-5p)、环磷酸腺苷反应元件结合蛋白1(CREB1)mRNA表达变化,并探讨其临床意义。方法选择食管癌患者92例,取手术切除的食管癌组织及其配对的癌旁正常组织,采用RT-qPCR技术检测miR-122-5p、CREB1 mRNA表达。比较食管癌组织与癌旁正常组织miR-122-5p、CREB1 mRNA表达差异,分析食管癌组织miR-122-5p表达与CREB1 mRNA表达的关系以及二者表达与患者临床病理特征的关系。所有患者术后定期随访3年,统计术后3年总生存率,比较食管癌组织不同miR-122-5p、CREB1 mRNA表达者术后3年总生存率差异。采用Cox比例风险回归模型分析食管癌患者预后不良的危险因素。结果食管癌组织miR-122-5p相对表达量明显低于癌旁正常组织,CREB1 mRNA相对表达量明显高于癌旁正常组织(t分别为-22.481、18.004,P均<0.01)。食管癌组织miR-122-5p表达与CREB1 mRNA表达呈负相关关系(r=-0.562,P<0.01)。食管癌组织miR-122-5p、CREB1 mRNA表达均与TNM分期、淋巴结转移有关(P均<0.05),而与性别、年龄、病理类型、肿瘤直径、组织分化程度无关(P均>0.05)。所有患者术后随访3年,随访期间死亡38例。以食管癌组织miR-122-5p、CREB1 mRNA相对表达量的均数为临界值,将患者分为miR-122-5p高表达者(≥0.346,44例)与低表达者(<0.346,48例)、CREB1 mRNA高表达者(≥3.488,42例)与低表达者(<3.488,50例),miR-122-5p高表达者术后3年总生存率高于miR-122-5p低表达者,CREB1 mRNA高表达者术后3年总生存率低于CREB1 mRNA低表达者(χ^(2)分别为7.327、7.582,P均<0.01)。Cox比例风险回归分析发现,TNM分期Ⅲ、Ⅳ期及有淋巴结转移、CREB1 mRNA表达≥3.488为食管癌患者预后不良的独立危险因素,而miR-122-5p表达≥0.346为其独立保护因素(P均<0.05)。结论食管癌组织miR-122-5p表达下调、CREB1 mRNA表达上调,二者表达变化与TNM分期、淋巴结转移以及患者预后有关。

Objective To investigate the expression changes of microRNA-122-5 p( miR-122-5 p) and cyclic adenosine monophosphate-response element-binding protein 1( CREB1) mRNA in the esophageal cancer and their clinical significance. Methods Ninety-two patients with esophageal cancer were selected,and the resected esophageal cancer tissues and adjacent normal tissues were collected. The expression levels of miR-122-5 p and CREB1 mRNA were detected by RTq PCR. The expression levels of miR-122-5 p and CREB1 mRNA in the esophageal cancer and adjacent normal tissues were compared,and the relationship between miR-122-5 p expression and CREB1 mRNA expression in esophageal cancer and their relationship with clinicopathological characteristics of patients were analyzed. All patients were followed up regularly for 3 years. The 3-year survival was counted,and the 3-year overall survival rate of patients with different miR-122-5 p and CREB1 mRNA expression in esophageal cancer was compared. Cox proportional hazards regression model was used to analyze the prognostic factors of esophageal cancer patients. Results The relative expression of miR-122-5 p in the esophageal cancer tissues was significantly lower than that in the adjacent normal tissues,and the relative expression of CREB1 mRNA was significantly higher than that in the adjacent normal tissues( t =-22. 481 and 18. 004,respectively;both P < 0. 01).There was a negative correlation between the expression of miR-122-5 p and CREB1 mRNA in esophageal cancer( r =-0. 562,P < 0. 01). The expression of miR-122-5 p and CREB1 mRNA in the esophageal cancer was related to TNM stage and lymph node metastasis( both P < 0. 05),but not to gender,age,pathological type,tumor diameter or degree of tissue differentiation( all P > 0. 05). All patients were followed up for 3 years,during which 38 cases died. The patients were divided into patients with high expression of miR-122-5 p( ≥ 0. 346,44 cases) and patients with low expression( < 0. 346,48 cases),patients with high expression of CREB1 mRNA( ≥3. 488,42 cases) and patients with low expression( < 3. 488,50 cases). The 3-year overall survival rate of patients with high expression of miR-122-5 p was higher than that of those with low expression of miR-122-5 p,and the 3-year overall survival rate of patients with high expression of CREB1 mRNA was lower than that of those with low expression of CREB1 mRNA( χ^(2)= 7. 327 and 7. 582,respectively;both P < 0. 01). Cox proportional hazards regression analysis showed that TNM stage Ⅲ and Ⅳ,lymph node metastasis and CREB1 mRNA expression ≥ 3. 488 were independent risk factors for the prognosis of esophageal cancer patients,and miR-122-5 p expression ≥ 0. 346 was independent protective factor( all P < 0. 05). Conclusions The expression of miR-122-5 p is down-regulated and CREB1 mRNA is up-regulated in esophageal cancer. Their expression changes are related to TNM stage,lymph node metastasis and prognosis.