微小RNA-203在食管癌中的表达水平及其临床意义

Expression of microRNA-203 in esophageal carcinoma and its clinical significance

目的探讨微小RNA(miRNA,miR)-203在食管癌中的表达水平及其与临床病理特征和预后的关系。方法选取河南省人民医院2016年1月到2020年1月收集的109例食管癌和癌旁组织作为标本,采用转录组学和荧光定量聚合酶链反应(PCR)分析癌旁组织和食管癌中差异表达miRNA;选择差异表达显著的miR-203分析其表达水平与食管癌患者临床病理特征和预后的关系;蛋白质印迹法(Western blot)分析食管癌组织细胞增殖抗原(Ki-67)表达水平;分析miR-203水平与Ki-67的关系。计量数据比较采用t检验,相关性采用Pearson相关系数法。结果转录组学技术筛选癌旁组织和食管癌组织中差异表达miRNA 25个,其中miR-203差异最为显著,因此本研究选择miR-203作为研究靶点。癌旁组织中miR-203表达水平(1.09±0.11)明显高于食管癌组织miR-203表达水平(0.37±0.09),差异有统计学意义(t=3.109,P<0.05)。中高分化患者食管癌组织miR-203表达水平(1.21±0.14)明显高于低分化患者食管癌miR-203表达水平(0.61±0.13),差异有统计学意义(t=3.331,P<0.05)。Ⅰ~Ⅱ期患者食管癌组织miR-203表达水平(1.18±0.17)明显高于Ⅲ~Ⅳ期患者食管癌组织miR-203表达水平(0.53±0.12),差异有统计学意义(t=3.973,P<0.05)。无淋巴结转移患者食管癌组织miR-203表达水平(1.24±0.15)明显高于淋巴结转移患者食管癌组织miR-203表达水平(0.42±0.13),差异有统计学意义(t=3.973,P<0.05)。miR-203高表达患者中位生存时间为70.43个月[95%可信区间(CI):60.54~81.76个月]明显高于miR-203低表达组患者48.21个月(95%CI:40.48~61.69个月),差异有统计学意义(Log-Rank=3.905,P<0.05)。miR-203高表达患者术后3年生存率[58.33%(28/48)]高于低表达组患者术后3年生存率[32.79%(20/61)],差异有统计学意义(Log-Rank=4.210,P<0.05)。miR-203高表达患者食管癌组织Ki-67表达水平(1.29±0.16)明显低于miR-203低表达患者(3.21±0.31),差异有统计学意义(t=5.116,P<0.05)。多因素Logistic回归显示食管癌患者3年生存率与临床分期、分化程度、临床分期、淋巴结转移、miR-203和Ki-67表达呈相关性[比值比(OR)=1.698、1.302、1.098、1.243、1.549、1.792,P<0.05]。结论miR-203在食管癌呈低表达,与患者临床病理特征和预后及其食管癌细胞增殖密切相关。

Objective To investigate the expression level of microRNA(miRNA,miR)-203 in esophageal carcinoma and its relationship with clinicopathological features and prognosis.Methods Totally,109 cases of esophageal cancer and adjacent tissues were collected in our hospital from January 2016 to January 2020 as samples.The differentially expressed miRNAs in esophageal cancer and adjacent tissues were analyzed by transcriptomics and fluorescence quantitative polymerase chain reaction(PCR).MiR-203 with significant differential expression was selected to analyze the relationship between its expression level and clinicopathological features and prognosis of patients with esophageal cancer.The expression of cell proliferation cell nuclear antigen(Ki-67)in esophageal carcinoma was analyzed by Western blotting.The relationship between miR-203 level and Ki-67 was analyzed.The measurement data were compared by t-test,and the Pearson correlation coefficient method was used for correlation.Results A total of 25 miRNAs were differentially expressed in esophageal cancer tissues and adjacent tissues by transcriptome technology and the difference of miR-203 was the most significant.Therefore,miR-203 was selected as the research target in this study.The expression level of miR-203 in adjacent tissues(1.09±0.11)was significantly higher than that in esophageal cancer tissues(0.37±0.09,t=3.109,P<0.05).The expression level of miR-203 in moderately and highly differentiated patients with esophageal cancer(1.21±0.14)was significantly higher than that in poorly differentiated patients(0.61±0.13,t=3.331,P<0.05).The expression level of miR-203 in esophageal cancer tissues of stageⅠ-Ⅱpatients(1.18±0.17)was significantly higher than that of stageⅢ-Ⅳpatients(0.53±0.12,t=3.973,P<0.05).The expression level of miR-203 in esophageal cancer without lymph node metastasis(1.24±0.15)was significantly higher than that in esophageal cancer with lymph node metastasis(0.42±0.13,t=3.973,P<0.05).The median survival time of patients with high expression of miR-203 was 70.43 months[95%confidence interval(CI):60.54-81.76 months],which was significantly longer than 48.21 months(95%CI:40.48-61.69 months)in patients with low expression of miR-203(Log rank=3.905,P<0.05).The 3-year survival rate of patients with high expression of miR-203[58.33%(28/48)]was significantly higher than that of patients with low expression of miR-203[32.79%(20/61),Log rank=4.210,P<0.05].The expression level of Ki-67 in esophageal cancer tissues of patients with high expression of miR-203(1.29±0.16)was significantly lower than that of patients with lower expression of miR-203(3.21±0.31,t=5.116,P<0.05).Multivariate logistic regression showed that the 3-year survival rate of patients with esophageal cancer was correlated with clinical stage,degree of differentiation,clinical stage,lymph node metastasis,miR-203 and Ki-67 expression[odds ratio(OR)=1.698,1.302,1.098,1.243,1.549,1.792,P<0.05].Conclusion The low expression of miR-203 in esophageal cancer is closely related to the clinicopathological features,prognosis and esophageal cancer cell proliferation.