A Pilot Study of Proteomic Profiles of Human Hepatocellular Carcinoma in the United States

被引:34
作者
Matos, Jesus M.
Witzmann, Frank A. [2 ]
Cummings, O. William [3 ]
Schmidt, C. Max [1 ,4 ,5 ,6 ,7 ]
机构
[1] Indiana Univ, Sch Med, Dept Surg, Canc Res Inst, Indianapolis, IN 46202 USA
[2] Indiana Univ, Sch Med, Dept Cellular & Integrat Physiol, Indianapolis, IN 46202 USA
[3] Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA
[4] Walther Oncol Ctr, Indianapolis, IN USA
[5] Indiana Univ, Sch Med, Ctr Canc, Indianapolis, IN 46202 USA
[6] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA
[7] Richard L Roudebush VA Med Ctr, Indianapolis, IN USA
关键词
hepatocellular carcinoma; liver; proteomics; cirrhosis; DIFFERENCE GEL-ELECTROPHORESIS; SEQUENCE-ANALYSIS; HEPATITIS; PROTEINS; IDENTIFICATION; EPIDEMIOLOGY; REVEALS; VIRUS;
D O I
10.1016/j.jss.2008.06.008
中图分类号
R61 [外科手术学];
学科分类号
100210 [外科学];
摘要
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.
引用
收藏
页码:237 / 243
页数:7
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