张建东,贺利民,马 磊.miR-21、PDCD4表达对Ⅱ期食管鳞癌术后患者生存期的影响[J].肿瘤学杂志,2017,23(12):1047-1054.
miR-21、PDCD4表达对Ⅱ期食管鳞癌术后患者生存期的影响
The Effect of MiR-21 and PDCD4 Expression on the Survival of Patients with Stage Ⅱ Esophageal Carcinoma After Operation
投稿时间:2017-06-05  
DOI:10.11735/j.issn.1671-170X.2017.12.B001
中文关键词:  食管鳞癌  miR-21  PDCD4  生存期  预后
英文关键词:esophageal squamous cell carcinoma  miR-21  PDCD4  survival  prognosis
基金项目:
作者单位
张建东 南阳市第一人民医院 
贺利民 南阳市第一人民医院 
马 磊 南阳市第一人民医院 
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中文摘要:
      摘 要:[目的] 探讨微小RNA 21(microRNA-21,miR-21)和细胞程序性死亡蛋白(programmed cell death protein 4,PDCD4)在Ⅱ期食管鳞癌术后患者癌组织中表达,分析其与临床病理特征的关系及对预后的影响。[方法] 收集胸中段Ⅱ期食管癌术后患者标本97例,将样本组织脱蜡提取总RNA;应用实时免疫荧光定量聚合酶链反应(RT-PCR)法检测所有标本癌组织、癌旁组织miR-21的表达情况;免疫组化法检测测癌组织和癌旁组织PDCD4蛋白表达水平。 [结果] miR-21在Ⅱ期食管鳞癌术后患者癌组织中的表达较癌旁组织升高(t=12.06,P<0.01),PDCD4在癌组织中的表达较癌旁组织降低(t=8.36,P<0.01)。miR-21和PDCD4在癌组织中的表达呈负相关(r=-0.41,P<0.01),在癌旁组织中的表达呈正相关(r=0.51,P<0.01)。癌组织中miR-21的表达与食管鳞癌的浸润深度、淋巴结转移、内镜下病变长度呈正相关(r=0.23,P=0.02;r=0.22,P=0.03;r=0.38,P<0.01)、与分化程度呈负相关(r=-0.60,P<0.01),PDCD4蛋白的表达与食管鳞癌的浸润深度、淋巴结转移、内镜下病变长度负相关(r=-0.21,P=0.04;r=-0.24,P=0.01;r=-0.37,P<0.01)、与分化程度呈正相关(r=0.53,P<0.01),二者与年龄、性别、位置不相关(P>0.05)。COX回归模型发现Ⅱ期食管鳞癌患者肿瘤浸润深度、淋巴结转移、分化程度、内镜下病变长度、miR-21表达、PDCD4表达均为影响患者PFS的因素(?字2=10.36,P=0.01;?字2=7.89,P<0.01;?字2=6.48,P=0.02;?字2=5.32,P=0.03;?字2=9.56,P=0.01;?字2=5.40,P=0.02)。miR-21对于术后3年PFS、OS预测曲线下面积分别为73.5%、81.0%(P<0.01);PDCD4对于术后3年PFS、OS预测曲线下面积分别为77.3%、73.2%(P<0.01)。miR-21、PDCD4高、低表达组PFS差异有统计学意义(?字2=19.6,P<0.01;?字2=11.45,P<0.01),OS差异也有统计学意义(?字2=27.84,P<0.01;?字2=21.35,P<0.01)。[结论]Ⅱ期食管鳞癌术后患者癌组织与癌旁正常组织中miR-21、PDCD4蛋白表达存在明显差异。高表达miR-21提示预后较差,而高表达PDCD4提示预后较好。
英文摘要:
      Abstract:[Objective] To study the expression of RNA-21 (microR-21 or miR-21) and PDCD4 (programmed cell death protein 4) in patients with stage Ⅱ esophageal squamous cell carcinoma after operation. To analyze the correlations among microR-21,PDCD4 and clinicopathological features as well as the effect of their expression on prognosis. [Methods] A total of 97 samples were collected from the mid-thoracic portion of patients with stage Ⅱ esophageal squamous cell carcinoma. Total RNA of these sample tissues was extracted by dewaxing. The expression level of miR-21 in all sample cancer tissues and adjacent tissues was detected by RT-PCR (real-time immunofluorescence quantitative polymerase chain reaction). And the expression level of PDCD4 in cancer tissues and adjacent normal tissues was detected by immunohistochemistry. [Results] The expression of miR-21 in cancer tissues was higher than that in adjacent normal tissues (t=12.06,P<0.01),and the expression of PDCD4 protein in cancer tissues was lower than that in adjacent normal tissues (t=8.36,P<0.01). The correlation analysis revealed a negative correlation (r=-0.41,P<0.01) of the expression of miR-21 and PDCD4 in cancer tissues and a positive correlation (r=0.51,P<0.01 )of their expression in adjacent normal tissues. The expression of miR-21 in cancer tissues was positively correlated with the depth of tumor invasion,lymph node metastasis and endoscopic lesion length (r=0.23,P=0.02;r=0.22;P=0.03;r=0.38;P<0.01),and negatively correlated with the differentiation degree(r=-0.60,P<0.01). The expression of PDCD4 protein in cancer tissues was negatively correlated with the depth of tumor invasion,lymph node metastasis and endoscopic lesion length(r=-0.21,P=0.04;r=-0.24,P=0.01;r=-0.37,P<0.01),and positively correlated with the differentiation (r=0.53,P<0.01). The expression of both was not correlated with age,gender and location(P>0.05). A COX regression model was established to reveal that the depth of tumor invasion,lymph node metastasis,differentiation degree,endoscopic lesion length,expression of microR-21 and expression of PDCD4 were all factors that affect PFS of patients with stage Ⅱ esophageal squamous cell carcinoma after operation(X2=10.36,P=0.01;X2=7.89,P<0.01;X2=6.48,P=0.02;X2=5.32,P=0.03,X2=9.56,P=0.01;X2=5.40,P=0.02,respectively). For miR-21,the area under the 3-year PFS and OS prediction curve was 73.5% and 81.0%,respectively(all P<0.01). For PDCD4,the area under the 3-year PFS and OS prediction curve was 77.3% and 73.2%,respectively expression. According to the cutoff values,different expression results of miR-21 and PDCD4 were divided into high and low expression groups. Kaplan-Meier was used to find that different expression of miR-21 and PDCD4 were significantly different in PFS(the results were X2=19.6,P<0.01;X2=11.45,P<0.01) and in OS(X2=27.84,P<0.01;X2=21.35,P<0.01). [Conclusion]There were significant differences in the expression of miR-21 and PDCD4 protein between cancerous tissues and adjacent normal tissues in patients with stage Ⅱ esophageal squamous cell carcinoma after operation. Highly expressed miR-21 suggested poor prognosis,while the high expression of PDCD4 protein suggested better prognosis.
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