miR-221与E-cadherin在肾透明细胞癌中的表达及临床意义

Expression and Clinical Significance of miR-221 and E-cadherin in Renal Clear Cell Carcinoma

目的研究miR-221及E-cadherin在肾透明细胞癌中的表达并分析两者的相关性,探讨miR-221表达对肾癌患者生存时间的影响以及预后的关系。方法选取经病理确诊的38例肾透明细胞癌患者为研究对象,手术后收集癌组织标本作为实验组,同时收集癌旁正常组织标本作为对照组,采用实时荧光定量PCR的方法分别检测实验组及对照组中miR-221的表达,分析miR-221与肾透明细胞癌患者临床病理参数的关系。对癌组织及癌旁组织病理切片进行免疫组织化学染色并检测E-cadherin的表达情况,分析E-cadherin与肾透明细胞癌患者临床病理参数之间的关系。Spearman相关性分析E-cadherin的表达与miR-221表达的相关性。Kaplan-Meier生存分析和log-rank检验评估肾透明细胞癌患者癌组织中miR-221表达与患者生存预后的关系。结果实验组中miR-221表达量(4.911±1.064)高于对照组(1.163±0.238),差异有统计学意义(P<0.05)。癌组织中,miR-221的相对表达量与Fuhrman分级、淋巴结转移有关(P<0.05),与年龄、性别、肿瘤大小、肾静脉内癌栓无关(P>0.05)。免疫组织化学染色结果显示E-cadherin在实验组中表达阳性率为26.32%(10/38),对照组表达阳性率为81.58%(31/38),两组表达差异有统计学意义(P<0.05)。E-cadherin的表达与年龄、性别、肿瘤大小、淋巴结转移、癌栓形成无关(P>0.05),与Fuhrman分级有关(P<0.05)。Spearman相关性分析结果显示E-cadherin的表达与miR-221的表达呈负相关,相关系数r为-0.569(P<0.001)。Kaplan-Meier生存曲线研究miR-221的表达与患者生存时间的关系,结果显示miR-221高表达组5 a生存率为52.94%(9/17),miR-221低表达组5 a生存率80.95%(17/21),log-rank检验评估miR-221高表达组与miR-221低表达组生存曲线的差异,结果显示差异有统计学意义(P<0.05)。结论miR-221在肾细胞癌中表达升高且与临床Fuhrman分级及淋巴结转移有关,miR-221与上皮-间质转化(EMT)相关分子E-cadherin的表达有相关性。本研究表明miR-221在肾透明细胞癌EMT进展过程中发挥一定的作用,是肾透明细胞癌患者生存及预后评估的潜在标志物。

Objective To investigate the expression of miR-221 and E-cadherin in renal clear cell carcinoma and analyze their correlation,then explored the relationship between the expression of miR-221 and the survival time and prognosis of renal cell cancer patients.Methods Thirty-eight patients with renal clear cell carcinoma diagnosed by pathology were selected as the research objects,and cancer tissue samples were collected after surgery as the experimental group.At the same time,the normal tissue samples were collected as the control group.Real-time quantitative PCR was used to detect the expression level of miR-221 in the experimental group and the control group.Then,the relationship between miR-221 and pathological characteristics of renal clear cell carcinoma patients was analyzed.Immunohistochemical staining was performed on the pathological sections to explore the expression of E-cadherin in cancer tissues and corresponding adjacent tissues.The relationship between E-cadherin and clinicopathological characteristics of patients with renal clear cell carcinoma was analyzed.The correlation between the expression of E-cadherin and the expression of miR-221 was analyzed by Spearman correlation analysis.Kaplan-Meier survival analysis and log-rank test were used to evaluate the relationship between the expression level of miR-221 in cancer tissues of patients with clear cell renal cell carcinoma and the prognosis of patients’survival.Results The expression of miR-221 in experimental group(4.911±1.064)was higher than that in the control group(1.163±0.238),and the difference was statistically significant(P<0.05).In cancer tissue specimens the relative expression of miR-221 was related to Fuhrman grade and lymph node metastasis(P<0.05),but not to age,gender,tumor size and tumor thrombus(P>0.05).The results of immunohistochemistry showed that the expression positive rate of E-cadherin in the experimental group was 26.32%(10/38),and the expression positive rate in the control group was 81.58%(31/38),there was a statistically significant difference between the two groups(P<0.05).The expression of E-cadherin was not related to age,gender,tumor size,lymph node metastasis,tumor thrombus formation(P>0.05),but was related to Fuhrman grade(P<0.05).The results of Spearman correlation analysis showed that the expression of E-cadherin was negatively correlated with the expression of miR-221,the correlation coefficient r was-0.569(P<0.001).The Kaplan-Meier survival curve was used to study the relationship between the expression of miR-221 and the survival time of patients.The results showed that the 5-year survival of the miR-221 high expression group was 52.94%(9/17),and the 5-year survival of the miR-221 low expression group was 80.95%(17/21).Log-rank test evaluated the difference in survival curve between the miR-221 high expression group and the miR-221 low expression group,and the results showed that the difference was statistically significant(P<0.05).Conclusion Increased expression of miR-221 in renal cell carcinoma is associated with clinical Fuhrman grading and lymph node metastasis,and miR-221 is associated with the expression of E-cadherin,a molecule associated with epithelial-mesenchymal transition(EMT).This study shows that miR-221 may plays a role in the progression of EMT in clear cell renal cell carcinoma,and is a potential marker for survival and prognosis assessment of clear cell renal cell carcinoma patients.