A Pilot Study of Proteomic Profiles of Human Hepatocellular Carcinoma in the United States
A Pilot Study of Proteomic Profiles of Human Hepatocellular Carcinoma in the United States
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DOI：
10.1016/j.jss.2008.06.008
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发表时间：
2009-08-01
影响因子：
2.2
通讯作者：
Schmidt, C. Max
中科院分区：
文献类型：
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作者：
Matos, Jesus M.;Witzmann, Frank A.;Schmidt, C. Max
人类肝细胞癌（HCC）是实体器官恶性肿瘤中最常见的死亡原因之一。HCC在美国的发病率正在上升。很少有蛋白质组学生物标志物研究在美国人群中进行。我们分析了3例美国肝炎和非肝炎相关性HCC患者的肿瘤和非恶性组织，以发现蛋白质表达的共同差异。用二维电泳（等电聚焦，然后用10% SDS-PAGE）分离蛋白质。凝胶固定后用考马斯亮蓝染色。利用PDQuest软件进行数字化处理。使用学生t检验来检测肿瘤和非恶性肝脏之间的定量蛋白质变化，所有样本对的截止值均为P < 0.01。这一共产生了20个点，丰度发生了显著的变化（bbb20倍）。采用Waters micromass M@LDI SYSTEM进行基质辅助激光解吸电离质谱分析。然后使用人工deep识别蛋白质。在20个斑点中，10个在肿瘤中呈过表达，10个呈低表达。过表达的蛋白包括β -5-微管蛋白、β -肌动蛋白、vimentin、癌2高甲基化蛋白、热休克70-kDa蛋白9B、血清白蛋白、39S核糖体蛋白L45、嗜丁酸蛋白、自身免疫调节因子和转录因子ETV7。低表达蛋白包括BiP蛋白、超氧化物歧化酶、过氧化物还氧蛋白2、无机焦磷酸酶、角蛋白8、碳酸酐酶1、排斥引导分子、过氧化氢酶、c -1-四氢叶酸合成酶和血红蛋白α -2。特别有趣的是，自身免疫调节蛋白在肿瘤组织中的表达高出14倍，表明它可能在HCC中起作用。对这些蛋白质变化的验证和进一步研究可能会导致发现新的治疗分子靶点，早期检测的生物标志物，以及治疗疗效和毒性的新终点。Elsevier Inc.出版。版权所有。
Human hepatocellular carcinoma (HCC) is one of the commonest causes of mortality among solid organ malignancies. The incidence of HCC in the United States is rising. Few proteomic biomarker studies have been done in U.S. populations. Tumor and nonmalignant tissue from three American patients with hepatitis and non-hepatitis-associated HCC were analyzed to find common differences in protein expression. Proteins were separated by 2D electrophoresis (isoelectric focusing followed by 10% SDS-PAGE). Gels were fixed and then stained with Coomassie brilliant blue. Digitization and processing were performed using the PDQuest software. The Student's t-test was used to detect quantitative protein changes between tumor and nonmalignant liver consistent in all sample pairs with a cutoff made at P < 0.01. This yielded a total of 20 spots with significant (>2 fold) abundance changes. Matrix-assisted laser desorption ionization mass spectrometry analysis was performed using Waters Micomass M@LDI SYSTEM. The proteins were then identified using manual ProFound. Among the 20 spots, 10 showed overexpression and 10 showed underexpression in tumor. Overexpressed proteins included beta-5-tubulin, beta-actin, vimentin, hypermethylated in cancer 2 protein, heat-shock 70-kDa protein 9B, serum albumin, 39S ribosomal protein L45, butyrophilin, autoimmune regulator, and transcription factor ETV7. Underexpressed proteins included BiP protein, superoxide dismutase, peroxiredoxin 2, inoraganic pyrophosphatase, keratin 8, carbonic anhydrase 1, repulsive guidance molecule, catalase, C-1-tetrahydrofolate synthase, and hemoglobin alpha-2. Of particular interest, the protein autoimmune regulator was expressed 14-fold higher in tumor tissue, suggesting it may have a role in HCC. Validation and further investigation of these protein changes may lead to the discovery of new molecular targets for therapy, biomarkers for early detection, and new endpoints for therapeutic efficacy and toxicity. Published by Elsevier Inc. All rights reserved.