结直肠癌组织中RREB1和ANKRD1的表达与临床病理特征和预后的相关性研究

Correlation between the Expression of RREB1 and ANKRD1 and Clinicopathological Features and Prognosis in Colorectal Cancer

目的探讨结直肠癌(colorectal cancer,CRC)组织ras反应元件结合蛋白1(ras-responsive element binding protein 1,RREB1),ankyrin重复结构域1(ankyrin repeat domain 1,ANKRD1)的表达及与临床病理特征和预后不良的关系。方法选取2013年1月~2016年12月复旦大学附属中山医院厦门医院收治的105例CRC患者,应用免疫组织化学SP法检测CRC患者癌组织和癌旁组织RREB1和ANKRD1蛋白表达,分析RREB1和ANKRD1蛋白表达与患者临床病理特征的关系,患者均随访5年,比较不同RREB1和ANKRD1表达患者的预后情况,并分析CRC患者预后不良的影响因素。采用Spearman相关系数分析RREB1与ANKRD1表达的相关性。结果CRC癌组织RREB1蛋白阳性率(59.05%)显著高于癌旁组织(27.61%),差异有统计学意义(χ^(2)=21.120,P=0.000)。CRC癌组织ANKRD1蛋白阳性率(31.43%)显著低于癌旁组织(60.95%),差异有统计学意义(χ^(2)=18.410,P=0.000)。TNM分期Ⅲ期、淋巴结转移N1~N2患者RREB1蛋白阳性率高于TNM分期Ⅰ~Ⅱ期、淋巴结转移N0患者,差异有统计学意义(χ^(2)=4.263,8.199,均P<0.05)。TNM分期Ⅲ期、淋巴结转移N1~N2患者ANKRD1蛋白阳性率低于TNM分期Ⅰ~Ⅱ期、淋巴结转移N0患者,差异有统计学意义(χ^(2)=5.515,7.411,均P<0.05)。RREB1高表达组5年生存率(54.84%)低于RREB1低表达组(74.42%),差异有统计学意义(χ^(2)=5.459,P=0.020);ANKRD1高表达组的5年生存率(78.79%)高于ANKRD1低表达组(55.56%),差异有统计学意义(χ^(2)=5.130,P=0.024)。RREB1高表达(HR=2.437,95%CI:1.113~4.684)、ANKRD1低表达(HR=0.573,95%CI:0.185~1.952)、TNM分期Ⅲ期(HR=2.202,95%CI:1.357~4.215)和淋巴结转移N1~N2(HR=1.247,95%CI:1.532~4.368)是CRC患者预后不良的危险因素(均P<0.05)。Spearman秩相关分析结果,CRC癌组织中RREB1与ANKRD1表达呈负相关(r=-0.389,P=0.036)。结论CRC癌组织中RREB1表达升高,而ANKRD1表达降低,二者共同参与CRC的发生发展,有望成为评估CRC患者预后的组织肿瘤标志物。

Objective To investigate the expression of ras response element-binding protein 1(RREB1)and ankyrin repeat domain 1(ANKRD1)in colorectal cancer(CRC)tissues and their relationship with clinicopathological features and poor prognosis.Methods A total of 105 CRC patients admitted to Xiamen Branch,Zhongshan Hospital Affiliated of Fudan University from January 2013 to December 2016 were selected and immunohistochemical SP method was used to detect the protein expression of RREB1 and ANKRD1 in CRC cancer tissue and paracancerous tissue.The relationship between RREB1and ANKRD1 protein expression and clinicopathological characteristics of patients was analyzed.All patients were followed up for 5 years,the prognosis of patients with different RREB1 and ANKRD1 expressions was compared,and the influencing factors of poor prognosis of CRC patients were analyzed.Spearman correlation coefficient was used to analyze the correlation between RREB1 and ANKRD1 expression.Results The positive rate of RREB1 protein in CRC cancer tissues(59.05%)which was significantly higher than in adjacent tissues(27.61%),and the difference was statistically significant(χ^(2)=21.120,P=0.000).The positive rate of ANKRD1 protein in CRC cancer tissues(31.43%)which was significantly lower than in adjacent tissues(60.95%),and the difference was statistically significant(χ^(2)=18.410,P=0.000).The positive rate of RREB1 protein in patients with TNM stageⅢand lymph node metastasis N1~N2 was higher than that in patients with TNM stageⅠ~Ⅱand lymph node metastasis N0,and the differences were statistically significant(χ^(2)=4.263,8.199,all P<0.05).The positive rate of ANKRD1 protein in patients with TNM stageⅢand lymph node metastasis N1~N2 was lower than that in patients with TNM stage I~II and lymph node metastasis N0,and the differences were statistically significant(χ^(2)=5.515,7.411,all P<0.05).The 5-year survival rate of RREB1 high expression group was 54.84%,which was lower than 74.42%of RREB1 low expression group,and the difference was statistically significant(χ^(2)=5.459,P=0.020).The 5-year survival rate of ANKRD1 high expression group was 78.79%,which was higher than 55.56%of ANKRD1 low expression group,and the difference was statistically significant(χ^(2)=5.130,P=0.024).High expression of RREB1(HR=2.437,95%CI:1.113~4.684),low expression of ANKRD1(HR=0.573,95%CI:0.185~1.952),TNM stageⅢ(HR=2.202,95%CI:1.357~4.215))and lymph node metastasis N1~N2(HR=1.247,95%CI:1.532~4.368)were risk factors for poor prognosis of CRC patients(all P<0.05).The results of Spearman rank correlation analysis showed that the expression of RREB1 and ANKRD1 in CRC cancer tissues was negatively correlated(r=-0.389,P=0.036).Conclusion The expression of RREB1 was increased in CRC cancer tissue,while the expression of ANKRD1 was decreased.Both of them were involved in the occurrence and development of CRC,and are expected to become tissue tumor markers for evaluating the prognosis of CRC patients.