结直肠癌组织中锌指蛋白139(ZNF139)的表达及临床意义研究

Expression and Clinical Significance of Zinc Finger Protein 139(ZNF139)in Colorectal Cancer

目的探究锌指蛋白139(zinc finger protein 139,ZNF139)在结直肠癌(colorectal cancer)组织中的表达及与临床病理参数及预后的关系。方法选取2012年5月~2014年6月就诊于恩施土家族苗族自治州中心医院行手术治疗的67例结直肠癌患者的临床病理资料及癌组织、癌旁组织和正常黏膜组织进行研究。采用实时荧光定量逆转录聚合酶链反应(RT-PCR)和免疫组织化学法染色检测ZNF139 mRNA及蛋白在结直肠癌组织中的表达情况,分析其与结直肠癌患者临床病理因素的关系;采用K-M生存曲线分析ZNF139表达对预后的影响;采用COX回归模型分析影响结直肠癌患者预后的风险因素。结果结直肠癌病灶组织中ZNF139 mRNA(0.651±0.130)表达水平明显高于癌旁组织(0.217±0.070)和正常组织(0.201±0.052),差异有统计学意义(t=24.060,24.947,均P=0.001)。结直肠癌组织中ZNF139蛋白阳性率(52.24%)明显高于癌旁组织(28.36%)和正常黏膜组织(19.40%),差异均有统计学意义(χ^(2)=7.941,15.711;P=0.005,0.000)。结直肠癌组织中ZNF139 mRNA及蛋白表达与肿瘤分化程度、浸润程度、TNM分期和有无淋巴结转移密切相关(t=4.447~10.964,χ^(2)=16.613~35.850,均P<0.01)。ZNF139阴性表达组患者5年总体生存率为75.0%,优于阳性组患者的51.4%(Log-rankχ^(2)=3.391,P=0.047)。ZNF139表达(HR:2.249,95%CI:1.359~3.712,P=0.003),临床TNM分期(HR:2.016,95%CI:1.230~3.327,P=0.006)和淋巴结转移(HR:2.125,95%CI:1.302~3.469,P=0.002)是影响结直肠癌患者总体预后的独立危险因素。结论ZNF139在结直肠癌组织中高(阳性)表达,与结直肠癌的分化、浸润、TNM分期和有无淋巴结转移密切相关,是影响结直肠癌患者预后的独立危险因素之一,可作为临床诊断及评估预后的参考指标。

Objective To investigate the relationship between the expression of zinc finger protein 139(ZNF139)in colorectal cancer tissues and the pathological parameters and prognosis of patients.Methods The clinicopathological data of 67 patients with colorectal cancer who received surgical treatment in Enshi Tujia and Miao Autonomous Prefecture Central Hospital from May 2012 to June 2014,as well as cancer tissue,para-cancer tissue and normal mucosal tissue,were selected for the study.Real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-PCR)and immunohistochemical staining were used to detect the expression of ZNF139 mRNA and protein in colorectal cancer tissues,and analyze its relationship with the clinicopathological factors of colorectal cancer patients.K-M survival curve was used to analyze the effect of ZNF139 expression on prognosis.Cox regression model was used to analyze the risk factors affecting the prognosis of colorectal cancer patients.Results The expression level of ZNF139 mRNA in colorectal cancer foci(0.651±0.130)was significantly higher than that in adjacent tissues(0.217±0.070)and normal tissues(0.201±0.052),the differences were statistically significant(t=24.060,24.947,all P=0.001).The positive rate of ZNF139 protein in colorectal cancer tissues(52.24%)was significantly higher than that in adjacent tissues(28.36%)and normal mucosa tissues(19.40%),the differences were statistically significant(χ^(2)=7.941,15.71,all P<0.01).The expression of ZNF139 mRNA and protein in colorectal cancer was closely related to the degree of tumor differentiation,invasion,TNM stage and lymph node metastasis(t=4.447~10.964,χ^(2)=16.613~35.850,all P<0.01).The 5-year overall survival rate of patients with negative expression of ZNF139 was 75.0%,which was better than that of patients with positive expression(51.4%)(Log-rankχ^(2)=3.391,P=0.047).ZNF139 expression(HR:2.249,95%CI:1.359~3.712,P=0.003),clinical TNM stage(HR:2.016,95%CI:1.223~3.327,P=0.006),lymph node metastasis(HR:2.125,95%CI:1.302~3.469,P=0.002)was an independent risk factor affecting the overall prognosis of colorectal cancer patients.Conclusion The high(positive)expression of ZNF139 in colorectal cancer tissues was closely related to the differentiation,infiltration,TNM stage and lymph node metastasis of colorectal cancer.It is an independent risk factor affecting the prognosis of colorectal cancer patients and can be used as a reference index for clinical diagnosis and prognosis evaluation.