Quantitative Proteomics Analysis of Tissue Interstitial Fluid for Identification of Novel Serum Candidate Diagnostic Marker for Hepatocellular Carcinoma.
Quantitative Proteomics Analysis of Tissue Interstitial Fluid for Identification of Novel Serum Candidate Diagnostic Marker for Hepatocellular Carcinoma.
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DOI：
10.1038/srep26499
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发表时间：
2016-05-24
影响因子：
4.6
通讯作者：
He F
中科院分区：
文献类型：
--
作者：
Sun W;Xing B;Guo L;Liu Z;Mu J;Sun L;Wei H;Zhao X;Qian X;Jiang Y;He F
肝细胞癌（HCC）是世界上第五大最常见的恶性肿瘤。甲胎蛋白（AFP）对于 HCC 诊断的敏感性仍然不足。组织间质液（TIF）作为癌细胞的液体微环境，在本研究中被用于生物标志物的发现。通过名为 iTRAQ（用于相对和绝对定量的同量异位标签）的蛋白质组学技术对来自 6 名 HBV-HCC 患者的配对肿瘤和非肿瘤 TIF 样本进行了分析。肿瘤 TIF 中总共鉴定出 241 个上调蛋白（比率≥ 1.3，p< 0.05）和 288 个下调蛋白（比率 ≤ −1.3，p< 0.05）。有趣的是，S100 家族的蛋白质在肿瘤 TIF 中显着上调。通过 ELISA 在肝硬化（LC、HCC 高危人群）和 HCC 患者（每组 n=≥47）的血清中进一步验证了一种显着上调的蛋白 S100A9（比率≥19）。与 LC 相比，HCC 血清中该蛋白的水平显着升高 (p<<0.0001)。该蛋白区分 HCC 和 LC 的曲线下面积为 0.83，敏感性为 91%（高于 AFP），特异性为 66%。这一结果证明了 S100A9 作为候选 HCC 诊断生物标志物的潜力。 TIF 是一种很有前景的材料，可用于识别可在血清中检测到的候选肿瘤生物标志物。
Hepatocellular carcinoma (HCC) is the fifth most common malignant cancer in the world. The sensitivity of alpha-fetoprotein (AFP) is still inadequate for HCC diagnosis. Tissue interstitial fluid (TIF), as the liquid microenvironment of cancer cells, was used for biomarker discovery in this study. Paired tumor and nontumor TIF samples from 6 HBV-HCC patients were analyzed by a proteomic technique named iTRAQ (isobaric tag for relative and absolute quantitation). Totally, 241 up-regulated proteins (ratio ≥ 1.3, p < 0.05) and 288 down-regulated proteins (ratio ≤ −1.3, p < 0.05) in tumor TIF were identified. Interestingly, proteins in S100 family were found remarkably up-regulated in tumor TIF. One dramatically up-regulated protein S100A9 (ratio = 19) was further validated by ELISA in sera from liver cirrhosis (LC, HCC high risk population) and HCC patients (n = 47 for each group). The level of this protein was significantly elevated in HCC sera compared with LC (p < 0.0001). The area under the curve of this protein to distinguish HCC from LC was 0.83, with sensitivity of 91% (higher than AFP) and specificity of 66%. This result demonstrated the potential of S100A9 as a candidate HCC diagnostic biomarker. And TIF was a kind of promising material to identify candidate tumor biomarkers that could be detected in serum.