Identification of novel immunohistochemical tumor markers for primary hepatocellular carcinoma; Clathrin heavy chain and formiminotransferase cyclodeaminase
Identification of novel immunohistochemical tumor markers for primary hepatocellular carcinoma; Clathrin heavy chain and formiminotransferase cyclodeaminase
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DOI：
10.1002/hep.22364
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发表时间：
2008-08-01
期刊：
影响因子：
13.5
通讯作者：
Nomura, Fumio
中科院分区：
文献类型：
--
作者：
Seimiya, Masanori;Tomonaga, Takeshi;Nomura, Fumio
肝细胞癌（HCC）的早期诊断大大改善了其预后。然而，良性和恶性肿瘤之间的区别往往是困难的，新的免疫组织化学标记物是必要的。应用琼脂糖双向荧光差异凝胶电泳技术，对10例肝癌组织进行了分析。与癌旁组织相比，48个斑点的荧光体积增加，79个斑点的荧光体积减少，质谱鉴定出83个蛋白质。免疫印迹证实，网格蛋白重链（CHC）和Ku 86的表达显着增加，而甲酰亚胺基转移酶环脱氨酶（FTCD），罗丹酸和黏着斑蛋白的表达下降。免疫组化染色进一步检测肿瘤组织和非肿瘤组织中蛋白的表达。有趣的是，CHC和FTCD的表达在肿瘤组织和非肿瘤组织之间存在显着差异。单项或联合检测CHC、FTCD和CHC+FTCD的敏感性和特异性分别为51.8%和95.6%、61.4%和98.5%、80.7%和94.1%。值得注意的是，当磷脂酰肌醇蛋白聚糖-3（另一种潜在的HCC生物标志物）与FTCD一起使用时，敏感性和特异性分别提高到86.7%和95.6%。CHC和FTCD对早期HCC与良性肿瘤如再生结节或局灶性结节性增生的鉴别诊断具有重要意义，其敏感性和特异性分别为41.2%和77.8%，FTCD分别为44.4%和80.0%，与磷脂酰肌醇蛋白聚糖-3的敏感性和特异性（33.3%和100%）相当。这些标记物的组合显著增加了敏感性，CHC+FTCD为72.2%，CHC+磷脂酰肌醇蛋白聚糖-3和FTCD+磷脂酰肌醇蛋白聚糖-3为61.1%，因为44.4%的磷脂酰肌醇蛋白聚糖-3阴性的早期HCC能够通过CHC或FTCD染色检测到。结论：CHC和FTCD的免疫组化染色对HCC的早期诊断有重要意义。
Early diagnosis of hepatocellular carcinoma (HCC) greatly improves its prognosis. However, the distinction between benign and malignant tumors is often difficult, and novel immunohistochemical markers are necessary. Using agarose two-dimensional fluorescence difference gel electrophoresis, we analyzed HCC tissues from 10 patients. The fluorescence volumes of 48 spots increased and 79 spots decreased in tumor tissues compared with adjacent nontumor tissue, and 83 proteins were identified by mass spectrometry. Immunoblot confirmed that the expression of clathrin heavy chain (CHC) and Ku86 significantly increased, whereas formiminotransferase cyclodeaminase (FTCD), rhodanese, and vinculin decreased in tumor. The protein expression in tumor and nontumor tissues was further evaluated by immunostaining. Interestingly, CHC and FTCD expression was strikingly different between tumor and nontumor tissues. The sensitivity and specificity of individual markers or a combination for the detection of HCC were 51.8% and 95.6% for CHC, 61.4% and 98.5% for FTCD, and 80.7% and 94.1% for CHC+FTCD, respectively. Strikingly, the sensitivity and specificity increased to 86.7% and 95.6% when glypican-3, another potential biomarker for HCC, was used with FTCD. Moreover, CHC and FTCD were useful to distinguish early HCC from benign tumors such as regenerative nodule or focal nodular hyperplasia, because the sensitivity and specificity of the markers are 41.2% and 77.8% for CHC, 44.4% and 80.0% for FTCD, which is comparable with those of glypican-3 (33.3% and 100%). The sensitivity significantly increased by combination of these markers, 72.2% for CHC+FTCD, and 61.1% for CHC+glypican-3 and FTCD+glypican-3, as 44.4% of glypican-3 negative early HCC were able to be detected by either CHC or FTCD staining. Conclusion: Immunostaining of CHC and FTCD could make substantial contributions to the early diagnosis of HCC.