Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma.
Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma.
复制标题
中期因子作为肝细胞癌诊断血清生物标志物的评价。
DOI：
10.1158/1078-0432.ccr-12-3363
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发表时间：
2013-07-15
期刊：
影响因子：
--
通讯作者：
Ye QH
中科院分区：
文献类型：
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作者：
Zhu WW;Guo JJ;Guo L;Jia HL;Zhu M;Zhang JB;Loffredo CA;Forgues M;Huang H;Xing XJ;Ren N;Dong QZ;Zhou HJ;Ren ZG;Zhao NQ;Wang XW;Tang ZY;Qin LX;Ye QH
评估血清midkine （MDK）作为肝细胞癌诊断生物标志物的价值，特别是对于甲胎蛋白（AFP）阴性和早期肝癌患者。采用免疫组化方法对105例肝细胞癌或肝硬化患者的MDK在肿瘤中的表达进行了评估。采用ELISA法检测了933名参与者的血清MDK水平，其中包括来自不同医疗中心的肝细胞癌患者和医院对照组。分析血清MDK根据甲胎蛋白水平和巴塞罗那临床肝癌分期诊断肝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显著升高。血清MDK对肝细胞癌诊断的敏感性远高于AFP(86.9%对51.9%)，特异性相似（83.9%对86.3%）。值得注意的是，血清MDK在区分不同对照的afp阴性肝细胞癌方面表现出色：在afp阴性肝细胞癌中，敏感性可高达89.2%。此外，受试者工作特征（ROC）曲线分析也显示，与AFP相比，血清MDK在鉴别早期肝细胞癌和小肝细胞癌方面有更好的表现。即使在非常早期的肝细胞癌中，MDK的敏感性也明显高于AFP（80%比40%）。此外，肝细胞癌患者在治愈性切除后血清MDK水平显著降低，肿瘤复发时血清MDK水平再次升高。血清MDK在大多数肝细胞癌（包括AFP阴性和早期）中显著升高，可作为肝细胞癌早期诊断和术后监测的一种新的诊断指标。
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.