Attallah Abdelfattah M, El-Far Mohamed, Malak Camelia A Abdel, Omran Mohamed M, Shiha Gamal E, Farid Khaled, Barakat Lamiaa A, Albannan Mohamed S, Attallah Ahmed A, Abdelrazek Mohamed A, Elbendary Mohamed S, Sabry Refaat, Hamoda Gehan A, Elshemy Mohamed M, Ragab Abdallah A, Foda Basma M, Abdallah Sanaa O
Biotechnology Research Center, P.O. Box (14), 23 July St., Industrial Zone, New Damietta, 34517, Egypt.
Faculty of Science, Mansoura University, Mansoura, Egypt.
Tumour Biol. 2015 Sep;36(10):7667-74. doi: 10.1007/s13277-015-3501-4. Epub 2015 May 1.
Currently, the search for suitable hepatocellular carcinoma (HCC) biomarkers is very intensive. Besides, efficacy and cost/effectiveness of screening and surveillance of cirrhotics for the diagnosis of HCC is still debated. So, the present study is concerned with the evaluation of cytokeratin-1 (CK-1) and nuclear matrix protein-52 (NMP-52) for identifying HCC. Two-hundred and eighty individuals categorized into three groups [liver fibrosis (F1-F3), cirrhosis (F4), and HCC] constituted this study. Western blot was used for identifying CK-1 and NMP-52 in serum samples. As a result, a single immunoreactive band was shown at 67 and 52 kDa corresponding to CK-1 and NMP-52, respectively. Both CK-1 and NMP-52 bands were cut and electroeluted separately. These markers were quantified in sera using ELISA. Patients with HCC were associated with higher concentrations of CK-1 and NMP-52 than those without HCC with a significant difference (P < 0.0001). CK-1 showed an area under receiver-operating characteristic curve (AUC) of 0.83 with 75 % sensitivity and 82 % specificity while NMP-52 yielded 0.72 AUC with 62 % sensitivity and 70 % specificity for identifying HCC. HCC-DETECT comprising CK-1 and NMP-52 together with AFP was then constructed yielding 0.90 AUC for identifying HCC with 80 % sensitivity and 92 % specificity. HCC-DETECT was then tested for separating HCC from F1-F3 showing 0.94 AUC with 80 % sensitivity and 93 % specificity. In conclusion, CK-1 in conjunction with NMP-52 and AFP could have a potential role for improving the detection of HCC with a high degree of accuracy.
目前，对合适的肝细胞癌（HCC）生物标志物的研究非常深入。此外，针对肝硬化患者进行HCC筛查和监测的有效性及成本效益仍存在争议。因此，本研究旨在评估细胞角蛋白-1（CK-1）和核基质蛋白-52（NMP-52）用于识别HCC的价值。本研究纳入了280名个体，分为三组[肝纤维化（F1-F3）、肝硬化（F4）和HCC]。采用蛋白质印迹法检测血清样本中的CK-1和NMP-52。结果显示，分别在67 kDa和52 kDa处出现一条与CK-1和NMP-52相对应的免疫反应条带。将CK-1和NMP-52条带分别切下并进行电洗脱。使用酶联免疫吸附测定法（ELISA）对血清中的这些标志物进行定量。与无HCC的患者相比，HCC患者的CK-1和NMP-52浓度更高，差异有统计学意义（P < 0.0001）。CK-1的受试者工作特征曲线（ROC）下面积（AUC）为0.83，灵敏度为75%，特异性为82%；而NMP-52识别HCC的AUC为0.72，灵敏度为62%，特异性为70%。然后构建了由CK-1、NMP-52和甲胎蛋白（AFP）组成的HCC-DETECT模型，其识别HCC的AUC为0.90，灵敏度为80%，特异性为92%。随后对HCC-DETECT模型进行测试，以区分HCC与F1-F3，其AUC为0.94，灵敏度为80%，特异性为93%。总之，CK-1联合NMP-52和AFP在提高HCC检测准确性方面可能具有潜在作用。
