Heat-shock protein 27: A potential biomarker for hepatocellular carcinoma identified by serum proteome analysis

Heat-shock protein 27: A potential biomarker for hepatocellular carcinoma identified by serum proteome analysis
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DOI:
10.1002/pmic.200401309
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发表时间:
2005-11-01
期刊:
影响因子:
3.4
通讯作者:
Tang, ZY
Tang, ZY
中科院分区:
生物学3区
文献类型:
--
作者:
Feng, JT;Liu, YK;Tang, ZY

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肝细胞癌(HCC)是全球第三大癌症死亡原因,在中国居第二位。肝细胞癌的预后仍然很差,主要是因为它的诊断晚,特别是在并存慢性肝病的患者。为了鉴定HCC的血清生物标志物,选择来自20名健康志愿者、20名B型肝炎病毒(HBV)感染者和20名HCC患者的血清进行筛选研究,并将相同数量的血清用于相同三组的验证研究。采用超声破碎、白蛋白和免疫球蛋白G(IgG)去除和酶切的方法筛选血清中低丰度差异表达蛋白。经双向电泳和MALDI-TOF-MS/MS鉴定,发现热休克蛋白27(HSP 27)、甲胎蛋白(AFP)、α 1抗胰蛋白酶、凝集素、铜蓝蛋白酶、触珠蛋白α 2链、转铁蛋白和转甲状腺素蛋白等8种蛋白质在健康人、HBV和HCC组中有明显变化。进一步的Western blot检测显示,90%的HCC血清和2份HBV血清中检测到HSP 27,而正常血清中未检测到HSP 27。因此,基于2-DE的血清蛋白质组分析可用于筛选HCC的血清生物标志物,HSP 27可辅助HCC的诊断,但需要进一步验证。
Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide and ranks second in China. The prognosis of H CC remains dismal mainly because of its late diagnosis, especially in patients with coexisting chronic liver diseases. To identify serum biomarkers for HCC, sera from 20 healthy volunteers, 20 hepatitis B virus (HBV) infected patients and 20 HCC patients were selected for screening study and same number of sera into the same three groups were used for validation study. A strategy including sonication, albumin and immunoglobulin G (IgG) depletion and desalting was optimized for screening differentially expressed proteins of low abundance in serum. By 2-DE image analysis and MALDI-TOF-MS/MS identification, eight proteins including heat-shock protein 27 (HSP27), alpha-fetoprotein (AFP), alpha-1 antitrypsin, clusterin, caeruloplasmin, haptoglobin alpha 2 chain, tranferrin and transthyretin were found significantly changed among the healthy, HBV and HCC groups. Further validation study by Western blot showed the detection of HSP27 in 90% HCC sera and two HBV sera, but in none of normal sera. Thus, 2-DE based serum proteome analysis can be useful in the screening of serum biomarkers for HCC and HSP27 could aid in the diagnosis of HCC though further validation is needed.