血清KLF5异常对良、恶性肝病诊断与鉴别诊断的临床价值

Clinical values of abnormal circulating KLF5 expression in diagnosis and differential diagnosis of patients with benign and malignant liver diseases

目的定量检测血液中锌指蛋白转录因子家族成员Krüppel样因子5(Krüppel-like factor 5,KLF5)的表达水平,分析对良、恶性、慢性肝病患者的诊断与鉴别诊断价值。方法经医院伦理委员会同意收集住院慢性肝炎(CH)患者40例、肝硬化(LC)患者40例、肝细胞癌(HCC)患者80例血液,以及健康体检正常人(NC)40份血清作为正常对照,以酶联免疫吸附分析(ELISA)定量测定血清KLF5水平,分析其临床病理学特征,并与血清AFP浓度比较,以评价对良、恶性肝病的诊断与鉴别诊断价值;经生物数据库资料分析KLF5的组织来源,并分析不同HCC细胞株中KLF5表达状态。结果在NC、CH、LC和HCC组患者血清中均可检出KLF5和AFP表达,显示血清KLF5和AFP浓度,在HCC组均显著高于LC组、CH组和NC组(P<0.001);如以血清KLF5>800 ng/ml和AFP>25 ng/ml为上界,其阳性率在HCC组分别为90.0%和68.8%,两者联检达93.8%;LC组为12.5%和32.5%;CH组为0和25.0%;NC组均未见阳性;诊断HCC受试者工作曲线(ROC)下面积,KLF5为0.88,优于AFP的0.76(P<0.001);KLF5和AFP诊断HCC灵敏度为90.0%和68.8%,特异度为85.1%和69.4%,准确度为88.4%和69.8%,阳性预测值为87.7%和54.8%,阴性预测值为88.1%和75.9%;生物信息库资料证明HCC组织中KLF5高表达,不同HCC细胞株中均见KLF5异常表达。结论KLF5为新的标志物,外周血中异常水平分析有助于HCC诊断及良、恶性肝病的鉴别诊断。

Objective To quantitatively measure the levels of circulating Krüppel-like factor 5(KLF5) expression of the Zinc finger protein transcription factor family for diagnosis and the differential diagnosis of patients with benign and malignant liver diseases.Methods The blood samples of 40 cases with chronic hepatitis(CH), 40 cases with liver cirrhosis(LC), and 80 cases with hepatocellular carcinoma(HCC) were collected by the consent of the Hospital Ethics Committee, with 40 cases of normal control(NC) as controls. Serum KLF5 level was measured by ELISA, and its clinical pathological characteristics were analyzed and compared with serum AFP level to evaluate the value of diagnosis or differential diagnosis of benign and malignant liver diseases. Tissue origins of KLF5 were confirmed by analyzing data of biological database, and the KLF5 expression status in different HCC cell lines were detected by Western blotting. Results The expression of KLF5 and AFP was detected in the sera of patients with NC, CH, LC and HCC. The concentrations of KLF5 and AFP in HCC were significantly higher than those in LC, CH and NC groups(P<0.001). When serum KLF5 >800 ng/ml and AFP level >25 ng/ml as normal upper values, the positive rates were 90.0% and 68.8% in HCC group, 12.5% and 32.5% in LC group, 0 and 25.0% in CH group, 0 in NC group, respectively. The area under receiver operating characteristic(ROC) curve of KLF5 was 0.88, better than that of AFP(0.76)(P<0.001), the sensitivity of KLF5 and AFP were 90.0% and 69.4%, specificity were 85.1% and 69.4%, accuracy were 88.4% and 69.8%, positive predictive value were 87.7% and 54.8%, negative predictive value were 88.1% and 75.9%,respectively. The biological information database showed that KLF5 was highly expressed in HCC tissues, and abnormal expression was found in all HCC cell lines. Conclusion Circulating KLF5 as a novel biomarker with abnormal expression might be helpful for HCC diagnosis or differential diagnosis of patients with benign and malignant liver diseases.