Large scale identification of human hepatocellular carcinoma-associated antigens by autoantibodies
Large scale identification of human hepatocellular carcinoma-associated antigens by autoantibodies
复制标题
DOI：
10.4049/jimmunol.169.2.1102
复制
发表时间：
2002-07-15
影响因子：
4.4
通讯作者：
Chen, WF
中科院分区：
文献类型：
--
作者：
Wang, Y;Han, KJ;Chen, WF
自身抗体经常在肝细胞癌 (HCC) 中检测到，这些反应可能代表对与转化事件相关的肿瘤抗原的识别。然而，这些Ag的身份却鲜为人知。通过对四名 HCC 患者的重组 cDNA 表达文库 (SEREX) 进行血清学分析，我们鉴定了 55 个可能编码 HCC 肿瘤 Ag 的独立 cDNA 序列。在这些基因中，有 15 个是新的。两种此类蛋白 HCA587 和 HCA661 主要在睾丸中检测到，但在其他正常组织中未检测到，除了在正常胰腺中表达较弱外。除了 HCC 之外，这两种 Ag 也可以在其他组织学类型的癌症中发现。因此，它们可以归类为癌症睾丸 (CT) Ag。另外两种 Ag（HCA519 和 HCA,90）在 HCC 中高度过表达，也在肺、前列腺和胰腺的癌细胞系中表达，但在各自的正常组织中不表达。其他四种 Ag 被鉴定为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、结肠癌细胞系和卵巢癌细胞系中的 HCA58），但在正常组织对应物中不表达。此外，在肝癌中还发现补体失活因子的大量表达。这些结果表明 HCC 患者中自身抗原的广泛表达。我们的研究结果为研究自身抗原在肝癌转化、转移和免疫逃避中的作用开辟了一条途径。
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 HCA,90) 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.