Quantitative Tissue Proteomics Analysis Reveals Versican as Potential Biomarker for Early-Stage Hepatocellular Carcinoma
Quantitative Tissue Proteomics Analysis Reveals Versican as Potential Biomarker for Early-Stage Hepatocellular Carcinoma
复制标题
DOI：
10.1021/acs.jproteome.5b00420
复制
发表时间：
2016-01-01
影响因子：
4.4
通讯作者：
Sitek, Barbara
中科院分区：
文献类型：
--
作者：
Naboulsi, Wael;Megger, Dominik A.;Sitek, Barbara
肝细胞癌（HCC）是最具侵袭性的肿瘤之一，早期诊断可以改善这种疾病的治疗效果。这就需要生物标志物来进行准确和早期的肿瘤诊断。为了确定此类应用的潜在标记物，我们使用两种独立的蛋白质组学方法分析了由50例患者组成的患者队列（50例HCC和50例邻近非肿瘤组织样本作为对照）。我们对19例HCC及相应的组织样本进行了无标签发现分析。数据分析考虑了HCC发展早期事件中已知的事件，如Wnt/b-catenin的异常调节和受体酪氨酸激酶（rtk）的激活。选取31个蛋白进行验证实验。在这项分析中，第二组患者队列（31例HCC和相应的组织样本）使用选择（多重）反应监测（SRM/MRM）进行分析。我们首次在HCC中发现atp依赖性RNA解旋酶（DDX39）、纤维蛋白-5 （FBLN5）、肉豆醇化富丙氨酸C-Idnase底物（MARCKS）和蛇形蛋白H1 （SERPINH1）的过表达。我们证明了Versican核心蛋白（VCAN）与高分化和低分期HCC显著相关。我们首次揭示了VCAN作为早期hcc诊断的潜在生物标志物的证据。
Hepatocellular carcinoma (HCC) is one of the most aggressive tumors, and the treatment outcome of this disease is improved when the cancer is diagnosed at an early stage. This requires biomarkers allowing an accurate and early tumor diagnosis. To identify potential markers for such applications, we analyzed a patient cohort consisting of 50 patients (50 HCC and 50 adjacent nontumorous tissue samples as controls) using two independent proteomics approaches. We performed label-free discovery analysis on 19 HCC and corresponding tissue samples. The data were analyzed considering events known to take place in early events of HCC development, such as abnormal regulation of Wnt/b-catenin and activation of receptor tyrosine kinases (RTKs). 31 proteins were selected for verification experiments. For this analysis, the second set of the patient cohort (31 HCC and corresponding tissue samples) was analyzed using selected (multiple) reaction monitoring (SRM/MRM). We present the overexpression of ATP-dependent RNA helicase (DDX39), Fibulin-5 (FBLN5), myristoylated alanine-rich C-Idnase substrate (MARCKS), and Serpin H1 (SERPINH1) in HCC for the first time. We demonstrate Versican core protein (VCAN) to be significantly associated with well differentiated and low-stage HCC. We revealed for the first time the evidence of VCAN as a potential biomarker for early-HCC diagnosis.