锌指蛋白转录因子Krüppel样因子5异常表达对肝细胞癌诊断及预后的价值

Value of abnormal expression of Krüppel-like zinc-finger protein transcription factor 5 in the diagnosis and prognosis of liver cancer

目的探讨锌指蛋白转录因子家族成员Krüppel样因子5(KLF5)对肝细胞癌(HCC)诊断与预后评估的价值。方法按自身配对法收集126例HCC术后癌及非癌组织(距离癌组织边缘3.0cm以上)制作芯片,以免疫组织化学法分析KLF5表达,并分析其表达的临床病理学特征及预后价值。收集222例慢性肝病患者血清并以酶联免疫吸附法(ELISA)定量测定其KLF5水平;以同期40例正常人血清为对照,以评价KLF5异常对良、恶性肝病诊断与鉴别诊断的价值。对数据进行t检验、Z检验或χ^(2)检验。结果HCC组KLF5表达阳性率为95.2%(120/126),显著高于非癌组的38.9%(49/126;χ^(2)=14.385,P<0.001)。KLF5表达与TNM分期(1期35%、II期40%、III期74.4%、IV期78.1%)、肿瘤大小、甲胎蛋白(AFP)水平、伴门静脉栓塞、HBV感染和患者5年生存率明显相关。单/多因素分析均显示KLF5高表达为HCC预后独立预测因素。HCC患者血清KLF5水平显著(P<0.001)高于肝硬化、慢性肝炎和正常对照组;如以血清KLF5>800 ng/ml和AFP>25μg/L为界,诊断HCC阳性率分别为90.48%和73.81%,比AFP特异、假阳性率低,有助于良、恶性肝病的鉴别诊断。结论HCC组织及血中KLF5过表达,它与HCC临床分期以及预后密切相关;分析KLF5水平有助于HCC诊断和鉴别诊断。

Objective To explore the value of Krippel-like factor 5(KLF5),a family member of the zinc finger protein transcription factor,in the diagnosis and prognostic evaluation of hepatocellular carcinoma(HCC).Methods Cancerous and non-cancerous tissues were collected from 126 cases after HCC surgery by self-matching method with microarray fabrication.Immunohistochemistry was used to analyze the expression of KLF5,clinicopathological characteristics and prognostic value.The sera of 222 cases with chronic liver disease were collected and their KLF5 levels were quantitatively determined by enzyme-linked immunosorbent assay(ELISA).Simultaneously,40 normal human sera were used as controls to evaluate the value of abnormal KLF5 in the diagnosis and differentiation of benign and malignant liver diseases.T-test,Z-test and χ^(2) test were performed on the data.Results The positive expression rate of KLF5 in the HCC group was 95.2%(120/126),which was significantly higher than the non-cancerous group 38.9%(49/126;χ^(2)=14.385,P<0.001).KLF5 expression was significantly correlated with TNM stage(stage I 35%,stage II 40%,stage III 74.4%,stage IV 78.1%),tumor size,alpha fetoprotein(AFP)concentration,portal vein embolism,HBV infection and 5-year survival rate.Univariate multivariate analysis showed that KLF5 high expression was an independent predictor of HCC prognosis.The serum KLF5 level was significantly higher in HCC patients than liver cirrhosis,chronic hepatitis and normal control group(P<0.001).With the serum KLF5>800 ng/ml and AFP>25 ug/L as limit,the positive rates for HCC diagnosis were 90.48%and 73.81%,respectively,which were lower than the AFP specificity and false positive rate,and was helpful for the differential diagnosis of benign and malignant liver diseases.Conclusion The overexpression of KLF5 in liver cancer tissues and blood is closely related to the HCC clinical stage and prognosis.Moreover,KLF5 analysis is helpful for HCC diagnosis and differential diagnosis.