miR-21、PDCD4表达对Ⅱ期食管鳞癌术后患者生存期的影响

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[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(χ~2=10.36,P=0.01;χ~2=7.89,P<0.01;χ~2=6.48,P=0.02;χ~2=5.32,P=0.03;χ~2=9.56,P=0.01;χ~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(X2=19.6,P<0.01;χ~2=11.45,P<0.01),OS差异也有统计学意义(χ~2=27.84,P<0.01;χ~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。 [Objective] To investigate the expression of microRNA-21, miR-21 and programmed cell death protein 4 (PDCD4) in patients with stage Ⅱ esophageal squamous cell carcinoma after surgery, and to analyze its relationship with clinical pathology Characteristics of the relationship and prognosis. [Method] Ninety-seven patients with stage Ⅱ esophageal carcinoma were collected and dewaxed to extract total RNA. All the specimens of cancerous tissue and paracancer tissues were detected by real-time immunofluorescence quantitative polymerase chain reaction (RT-PCR) The expression of miR-21 was detected by immunohistochemistry. The expression of PDCD4 in cancer tissues and adjacent tissues was detected by immunohistochemistry. [Results] The expression of miR-21 in stage II esophageal squamous cell carcinoma patients was significantly higher than that in adjacent non-cancerous tissues (t = 12.06, P <0.01), and the expression of PDCD4 in cancer tissues was lower than that in paracancerous tissues = 8.36, P <0.01). The expression of miR-21 and PDCD4 in cancer tissues was negatively correlated (r = -0.41, P <0.01), and positively correlated with the expression in adjacent tissues (r = 0.51, P <0.01). The expression of miR-21 in cancer tissues was positively correlated with the depth of invasion, lymph node metastasis and length of endoscopic lesions (r = 0.23, P = 0.02; r = 0.22, P = 0.03; ) Was negatively correlated with the degree of differentiation (r = -0.60, P <0.01). The expression of PDCD4 protein was negatively correlated with the depth of invasion, lymph node metastasis and endoscopic lesions (r = -0.21, P = 0.04 (r = -0.24, P = 0.01; r = -0.37, P <0.01), but positively correlated with the degree of differentiation (r = 0.53, . COX regression model found that the depth of tumor invasion, lymph node metastasis, differentiation degree, length of endoscopic lesions, miR-21 expression and PDCD4 expression in patients with stage II esophageal squamous cell carcinoma were the factors affecting the PFS (χ ~ 2 = 10.36, P = 0.01 χ2 = 7.89, P <0.01; χ2 = 6.48, P = 0.02; χ2 = 5.32, P = 0.03; χ2 = 9.56, P = ). The predicted area under the curve of OS was 73.5% and 81.0% respectively (P <0.01). The area under the predicted curve of PDCD4 for 3-year postoperative PFS and OS was 77.3% and 73.2% respectively <0.01). There were significant differences in PFS between miR-21 and PDCD4 high and low expression groups (χ 2 = 19.6, P <0.01; χ 2 = 11.45, P <0.01) <0.01; χ ~ 2 = 21.35, P <0.01). [Conclusion] The expression of miR-21 and PDCD4 in cancer tissue and adjacent normal tissue of patients with stage Ⅱ esophageal squamous cell carcinoma are significantly different. High expression of miR-21 prompted a poor prognosis, and high expression of PDCD4 prompted a better prognosis.
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