Attallah Abdelfattah M, El-Far Mohamed, Abdel Malak Camelia A, Farid Khaled, Omran Mohamed M, Yahya Raida S, Saad Entsar A, Albannan Mohamed S, Attallah Ahmed A, El Basuni Mohamed A, Ali Islam S, Abed Safaa B, El Naggar Mohamed A
Research & Development Department, Biotechnology Research Center, New Damietta City, Egypt.
Faculty of Science, Mansoura University, Mansoura, Egypt.
Ann Hepatol. 2015 Nov-Dec;14(6):869-80. doi: 10.5604/16652681.1171774.
Background and rationale for the study. Continuing search for suitable tumor-markers is of clinical value in managing patients with various malignancies. These markers may be presented as intracellular substances in tissues or may be released into the circulation and appear in serum. Therefore, this work is concerned with identification and quantitative determination of epithelial membrane antigen (EMA) and fibronectin and estimating their performances as surrogate markers for identifying hepatocellular carcinoma (HCC).
A total of 627 individuals constituted this study [fibrosis (F1-F3) = 217; cirrhosis = 191; HCC = 219]. Western-blot was used for identifying EMA and fibronectin in sera. As a result, a single immunoreactive band was shown at 130-kDa and 90-kDa corresponding to EMA and fibronectin, respectively. They were quantified using ELISA providing values in HCC higher than fibrosis or cirrhosis with a significant difference (P < 0.0001). For identifying HCC, EMA showed 0.82 area under receiver-operating characteristic curve (AUC) with sensitivity = 70% and specificity = 78% while fibronectin yielded AUC = 0.70 with sensitivity = 67% and specificity = 82%. FEBA-Test comprising fibronectin and EMA together with total-bilirubin and AFP was constructed yielding AUC = 0.92 for identifying HCC from cirrhosis with sensitivity = 89% and specificity = 85%. FEBA-Test was then tested for differentiating HCC from fibrosis showing AUC = 0.97 with sensitivity = 90% and specificity = 89%. FEBA-Test enabled the correct identification of HCC patients with CLIP 0-1 and size ≤ 3 cm with AUC = 0.80 and AUC = 0.84, respectively, indicating its ability in identifying early HCC.
A four-marker index may improve the early detection of HCC with a high degree of accuracy.
研究背景及原理。持续寻找合适的肿瘤标志物对于管理各类恶性肿瘤患者具有临床价值。这些标志物可能以组织内的细胞内物质形式存在，或者释放到循环系统中并出现在血清中。因此，本研究关注上皮膜抗原（EMA）和纤连蛋白的鉴定与定量测定，并评估它们作为肝细胞癌（HCC）替代标志物的性能。
本研究共纳入627名个体[纤维化（F1 - F3）= 217；肝硬化 = 191；HCC = 219]。采用蛋白质免疫印迹法鉴定血清中的EMA和纤连蛋白。结果显示，分别在130 kDa和90 kDa处出现一条对应于EMA和纤连蛋白的免疫反应条带。使用酶联免疫吸附测定法对其进行定量，结果显示HCC中的含量高于纤维化或肝硬化，差异具有统计学意义（P < 0.0001）。对于HCC的鉴别，EMA的受试者工作特征曲线下面积（AUC）为0.82，敏感性 = 70%，特异性 = 78%；而纤连蛋白的AUC = 0.70，敏感性 = 67%，特异性 = 82%。构建了包含纤连蛋白、EMA以及总胆红素和甲胎蛋白的FEBA检测法，用于从肝硬化中鉴别HCC时，AUC = 0.92，敏感性 = 89%，特异性 = 85%。然后对FEBA检测法进行测试，以鉴别HCC与纤维化，AUC = 0.97，敏感性 = 90%，特异性 = 89%。FEBA检测法能够正确鉴别CLIP 0 - 1且大小≤3 cm的HCC患者，AUC分别为0.80和0.84，表明其具有鉴别早期HCC的能力。
一种四标志物指标可能以高度准确性改善HCC的早期检测。
