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利用自身抗体大规模鉴定人类肝细胞癌相关抗原

Large scale identification of human hepatocellular carcinoma-associated antigens by autoantibodies.

作者信息

Wang Yu, Han Ke-Jun, Pang Xue-Wen, Vaughan Hilary A, Qu Wei, Dong Xue-Yuan, Peng Ji-Run, Zhao Hai-Tao, Rui Jing-An, Leng Xi-Sheng, Cebon Jonathan, Burgess Antony W, Chen Wei-Feng

机构信息

Immunology Department, School of Basic Medical Science, Peking University Health Science Center, Beijing, China.

出版信息

J Immunol. 2002 Jul 15;169(2):1102-9. doi: 10.4049/jimmunol.169.2.1102.

DOI:10.4049/jimmunol.169.2.1102
PMID:12097419
Abstract

Autoantibodies are often detected in hepatocellular carcinoma (HCC), and these responses may represent recognition of tumor Ags that are associated with transformation events. The identities of these Ags, however, are less well known. Using serological analysis of recombinant cDNA expression libraries (SEREX) from four HCC patients, we identified 55 independent cDNA sequences potentially encoding HCC tumor Ags. Of these genes, 15 are novel. Two such proteins, HCA587 and HCA661, were predominantly detected in testis, but not in other normal tissues, except for a weak expression in normal pancreas. In addition to HCC, these two Ags can be found in cancers of other histological types. Therefore, they can be categorized as cancer-testis (CT) Ags. Two other Ags (HCA519 and HCA90) were highly overexpressed in HCC and also expressed in cancer cell lines of lung, prostate, and pancreas, but not in the respective normal tissues. Four other Ags were identified to be expressed in particular types of cancer cell lines (HCA520 in an ovarian cancer cell line, HCA59 and HCA67 in a colon cancer cell line, HCA58 in colon and ovarian cancer cell lines), but not in the normal tissue counterpart(s). In addition, abundant expression of complement inactivation factors was found in HCC. These results indicate a broad range expression of autoantigens in HCC patients. Our findings open an avenue for the study of autoantigens in the transformation, metastasis, and immune evasion in HCC.

摘要

肝细胞癌(HCC)中常可检测到自身抗体,这些反应可能代表对与肿瘤转化事件相关的肿瘤抗原的识别。然而,这些抗原的具体身份尚不太清楚。通过对4例HCC患者的重组cDNA表达文库进行血清学分析(SEREX),我们鉴定出55个可能编码HCC肿瘤抗原的独立cDNA序列。其中15个是新基因。两种这样的蛋白,HCA587和HCA661,主要在睾丸中检测到,在其他正常组织中未检测到,但在正常胰腺中有微弱表达。除了HCC,这两种抗原也可在其他组织学类型的癌症中发现。因此,它们可归类为癌-睾丸(CT)抗原。另外两种抗原(HCA519和HCA90)在HCC中高度过表达,也在肺癌、前列腺癌和胰腺癌的癌细胞系中表达,但在各自的正常组织中不表达。另外鉴定出四种抗原在特定类型的癌细胞系中表达(卵巢癌细胞系中的HCA520、结肠癌细胞系中的HCA59和HCA67、结肠和卵巢癌细胞系中的HCA58),但在相应的正常组织中不表达。此外,在HCC中发现补体灭活因子的丰富表达。这些结果表明HCC患者自身抗原的广泛表达。我们的发现为研究HCC中的自身抗原在肿瘤转化、转移和免疫逃逸方面开辟了一条途径。

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