Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science, Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
Clin Cancer Res. 2013 Jul 15;19(14):3944-54. doi: 10.1158/1078-0432.CCR-12-3363. Epub 2013 May 29.
To evaluate the value of serum midkine (MDK) as a diagnostic biomarker in hepatocellular carcinoma, particularly for those with negative alpha-fetoprotein (AFP) and at an early stage.
MDK expression in tumors was assessed by immunohistochemistry from 105 patients with hepatocellular carcinomas or liver cirrhosis. Serum MDK levels were detected by ELISA in 933 participants including hepatocellular carcinomas and hospital controls from different medical centers. Sensitivities and specificities of serum MDK in diagnosing hepatocellular carcinoma according to AFP level and Barcelona Clinic Liver Cancer (BCLC) stage were analyzed.
MDK levels were significantly elevated in hepatocellular carcinoma tissues as well as serum samples. The sensitivity of serum MDK for hepatocellular carcinoma diagnosis was much higher than that of AFP (86.9% vs. 51.9%) with similar specificities (83.9% vs. 86.3%). Notably, serum MDK had an outstanding performance in distinguishing AFP-negative hepatocellular carcinomas from different controls: In those AFP-negative hepatocellular carcinomas, the sensitivity could reach as high as 89.2%. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MDK had a better performance compared with AFP in distinguishing early-stage hepatocellular carcinomas as well as small hepatocellular carcinomas. Even in very early-stage hepatocellular carcinomas, MDK showed an obviously higher sensitivity compared with AFP (80% vs. 40%). Furthermore, serum MDK level was significantly decreased in patients with hepatocellular carcinomas after curative resection and re-elevated when tumor relapse occurred.
Serum MDK is significantly elevated in most hepatocellular carcinomas, including those with negative AFP and at an early stage, which may serve as a novel diagnostic marker in early diagnosis and postoperative monitoring of hepatocellular carcinomas.
评估血清中期因子（MDK）作为肝细胞癌诊断生物标志物的价值，尤其是在甲胎蛋白（AFP）阴性和早期阶段。
通过免疫组织化学法从 105 例肝细胞癌或肝硬化患者的肿瘤中评估 MDK 表达。ELISA 法检测来自不同医疗中心的 933 例参与者（包括肝细胞癌和医院对照）的血清 MDK 水平。分析血清 MDK 根据 AFP 水平和巴塞罗那临床肝癌（BCLC）分期诊断肝细胞癌的敏感性和特异性。
MDK 水平在肝细胞癌组织和血清样本中均显著升高。血清 MDK 诊断肝细胞癌的敏感性明显高于 AFP（86.9% vs. 51.9%），特异性相似（83.9% vs. 86.3%）。值得注意的是，血清 MDK 在区分 AFP 阴性肝细胞癌与不同对照方面表现出色：在那些 AFP 阴性的肝细胞癌中，敏感性可高达 89.2%。此外，受试者工作特征（ROC）曲线分析还表明，血清 MDK 在区分早期肝细胞癌和小肝细胞癌方面优于 AFP。即使在非常早期的肝细胞癌中，MDK 也显示出比 AFP 更高的敏感性（80% vs. 40%）。此外，根治性切除术后肝细胞癌患者的血清 MDK 水平显著降低，当肿瘤复发时再次升高。
大多数肝细胞癌，包括 AFP 阴性和早期阶段的肝细胞癌，血清 MDK 水平均显著升高，这可能成为早期诊断和术后监测肝细胞癌的新型诊断标志物。
