食管癌根治术患者血清microRNA-27a、microRNA-203a-3p表达及与预后的关系

Relationship between serum expressions of miR-27a and miR-203a-3p and prognosis of patients undergoing radical resection for esophageal cancer

摘要:

目的 探究食管癌根治术患者术前血清microRNA-27a（miR-27a）、microRNA-203a-3p（miR-203a-3p）表达及与预后的关系。方法 选取2016年3月—2017年3月在南阳医学高等专科学校第一附属医院行食管癌根治术的123例食管癌患者作为研究组。另取同期该院健康体检人群64例作为对照组。采用实时荧光定量聚合酶链反应检测研究组术前和对照组体检时血清miR-27a、miR-203a-3p的表达。分析食管癌患者血清miR-27a、miR-203a-3p相对表达量与临床病理特征的关系。Kaplan-Meier生存曲线分析血清miR-27a、miR-203a-3p表达与患者预后的关系。单因素及多因素Cox回归分析食管癌患者预后的影响因素。结果 研究组血清miR-27a、miR-203a-3p相对表达量高于对照组（P <0.05）。肿瘤分期Ⅲ期、分化程度低分化、有淋巴结转移食管癌患者根治术前血清miR-27a、miR-203a-3p相对表达量高于肿瘤分期Ⅰ、Ⅱ期、分化程度高中分化、无淋巴结转移患者（P <0.05）。不同年龄、性别及肿瘤位置食管癌患者根治术前血清miR-27a、miR-203a-3p相对表达量比较，差异无统计学意义（P >0.05）。miR-27a高表达组5年总生存率低于miR-27a低表达组（P <0.05）。miR-203a-3p高表达组5年总生存率低于miR-203a-3p低表达组（P <0.05）。单因素Cox回归分析结果显示：肿瘤分期［H^R=1.730（95% CI：1.434，2.099）］、淋巴结转移［H^R=1.602（95% CI：1.191，2.153）］、miR-27a［H^R=2.041（95% CI：1.813，2.463）］、miR-203a-3p［H^R=2.060（95% CI：1.921，2.279）］是食管癌患者预后的影响因素（P <0.05）。多因素Cox回归分析结果显示：肿瘤分期Ⅲ期［H^R=1.973（95% CI：1.245，3.219）］、有淋巴结转移［H^R=2.637（95% CI：1.158，6.008）］、miR-27a ≥ 3.09［H^R=2.484（95% CI：1.435，4.301）］、miR-203a-3p ≥ 2.79［H^R=1.660（95% CI：1.236，3.058）］是食管癌患者预后的独立影响因素（P <0.05）。结论 食管癌患者血清miR-27a、miR-203a-3p表达上调，两者表达与肿瘤TNM分期、分化程度及淋巴结转移有关，是食管癌根治术患者预后不良的独立危险因素。

Abstract:

Objective To study the preoperative serum expressions of microRNA-27a (miR-27a) and microRNA-203a-3p (miR-203a-3p) in patients with esophageal cancer and their relationship with clinical outcomes of patients.Methods From March 2016 to March 2017, 123 patients with esophageal cancer who underwent radical resection for esophageal cancer in our hospital were selected as the study group. Another 64 healthy people who underwent health checkup during the same period were selected as the control group. The serum levels of miR-27a and miR-203a-3p before the operation in the study group and those during the health checkup in the control group were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between serum levels of miR-27a and miR-203a-3p and clinicopathological characteristics in patients with esophageal cancer was analyzed. Kaplan-Meier survival curves were used to analyze the relationship between serum levels of miR-27a and miR-203a-3p and the prognosis of patients. Univariate and multivariate COX regression analysis was performed to determine factors influencing prognosis of patients with esophageal cancer.Results The serum levels of miR-27a and miR-203a-3p in the study group were higher than those in the control group (P < 0.05). Besides, the serum levels of miR-27a and miR-203a-3p before the radical surgery in esophageal cancer patients with stage Ⅲ tumors, poorly differentiated tumors and lymph node metastasis were higher than those in esophageal cancer patients with stage Ⅰ to Ⅱ tumors, well differentiated tumors and no lymph node metastasis (P < 0.05). There was no difference in the serum levels of miR-27a and miR-203a-3p before the radical surgery in esophageal cancer patients with different age, sex and tumor location (P >0.05). The 5-year overall survival rate in the miR-27a high expression group was lower than that in the miR-27a low expression group (P < 0.05). The 5-year overall survival rate of patients with high miR-203a-3p expression was lower than that of patients with low miR-203a-3p expression group (P < 0.05). Univariate COX regression analysis showed that tumor stage [H^R = 1.730 (95% CI: 1.434, 2.099) ], lymph node metastasis [H^R= 1.602 (95% CI: 1.191, 2.153) ], miR-27a [H^R = 2.041 (95% CI: 1.813, 2.463) ] and miR-203a-3p [H^R = 2.060 (95% CI: 1.921, 2.279) ] were prognostic factors of patients with esophageal cancer (P < 0.05). Multivariate COX regression analysis showed that stage III tumor [H^R= 1.973 (95% CI: 1.245, 3.219) ], lymph node metastasis [H^R= 2.637 (95% CI: 1.158, 6.008)], the level of miR-27a≥ 3.09 [H^R= 2.484 (95% CI: 1.435, 4.301) ], and the level of miR-203a-3p ≥ 2.79 [H^R = 1.660 (95% CI: 1.236, 3.058) ] were independent risk factors affecting the prognosis of patients with esophageal cancer (P < 0.05).Conclusions The serum expressions of miR-27a and miR-203a-3p are up-regulated in patients with esophageal cancer, and their expressions are related to tumor TNM stage, degree of differentiation and lymph node metastasis. Besides, high expressions of miR-27a and miR-203a-3p are independent risk factors for poor prognosis of patients undergoing radical resection for esophageal cancer.