Secreted ERBB3 Isoforms Are Serum Markers for Early Hepatoma in Patients with Chronic Hepatitis and Cirrhosis
Secreted ERBB3 Isoforms Are Serum Markers for Early Hepatoma in Patients with Chronic Hepatitis and Cirrhosis
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DOI：
10.1021/pr200519q
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发表时间：
2011-10-01
影响因子：
4.4
通讯作者：
Chiu, Cheng-Tang
中科院分区：
文献类型：
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作者：
Hsieh, Sen-Yung;He, Jung-Ru;Chiu, Cheng-Tang
为寻找慢性肝炎和肝硬化患者早期肝癌的新标志物，我们采用差异凝胶电泳和抗体芯片技术，从肿瘤间质液（TIP）中筛选分泌型ERBB 3亚型（sERBB 3）。采用受试者工作特征曲线（ROC）分析血清sERBB 3在HCC诊断中的作用。肝癌患者血清sERBB 3水平显著高于肝硬化（p < 0.001）和慢性肝炎（p < 0.001）。在两组独立的患者中进一步验证了血清sERBB 3检测HCC的准确性。在区分早期HCC与慢性肝炎或肝硬化时，血清sERBB 3比甲胎蛋白（AFP）具有更好的性能（ROC下的面积[AUC]：sERBB 3 vs AFP = 93.1 vs 81.0%，来自慢性肝炎和70.9 vs 62.7%，来自肝硬化）。联合检测sERBB 3和AFP进一步提高了从慢性肝炎中检测早期HCC的准确性（AUC.; = 97.1%）或肝硬化（AUC = 77.5%）。血清sERBB 3水平升高与HCC的门静脉浸润和肝外转移相关（p = 0.017）。因此，sERBB 3是慢性肝炎和肝硬化患者早期HCC的血清标志物。
Most hepatocellular carcinoma (HCC) is generated from chronic hepatitis and cirrhosis, To discover new markers for early HCC in patients with chronic hepatitis and cirrhosis, we initiated our search in the interstitial fluid of tumor (TIP) via differential gel electrophoresis and antibody arrays and identified secreted ERBB3 isoforms (sERBB3). The performance of serum sERBB3 in diagnosis of HCC was analyzed using receiver operating characteristic curves (ROC). The serum sERBB3 level was significantly higher in HCC than in cirrhosis (p < 0.001) and chronic hepatitis (p < 0.001). The accuracy of serum sERBB3 in detection of HCC was further validated in two independent sets of patients. In discrimination of early HCC from chronic hepatitis or cirrhosis, serum sERBB3 had a better performance than alpha-fetoprotein (AFP) (areas under ROC [AUC]: sERBB3 vs AFP = 93.1 vs 81.0% from chronic hepatitis and 70.9 vs 62.7% from cirrhosis). Combination of sERBB3 and AFP further improved the accuracy in detection of early HCC from chronic hepatitis (AUC.; = 97.1%) or cirrhosis (AUC = 77.5%). Higher serum sERBB3 levels were associated with portal-vein invasion and extrahepatic metastasis of HCC (p = 0.017). Therefore, sERBB3 are serum markers for early HCC in patients with chronic hepatitis and cirrhosis.