Proteome Profiling Uncovers an Autoimmune Response Signature That Reflects Ovarian Cancer Pathogenesis

蛋白质组分析揭示反映卵巢癌发病机制的自身免疫反应特征

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作者:Makoto Kobayashi, Hiroyuki Katayama, Ehsan Irajizad, Jody V Vykoukal, Johannes F Fahrmann, Deepali L Kundnani, Chuan-Yih Yu, Yining Cai, Fu Chung Hsiao, Wei-Lei Yang, Zhen Lu, Joseph Celestino, James P Long, Kim-Ann Do, Karen H Lu, Jon J Ladd, Nicole Urban, Robert C Bast Jr, Samir M Hanash

Abstract

Harnessing the immune response to tumor antigens in the form of autoantibodies, which occurs early during tumor development, has relevance to the detection of cancer at early stages. We conducted an initial screen of antigens associated with an autoantibody response in serous ovarian cancer using recombinant protein arrays. The top 25 recombinants that exhibited increased reactivity with cases compared to controls revealed TP53 and MYC, which are ovarian cancer driver genes, as major network nodes. A mass spectrometry based independent analysis of circulating immunoglobulin (Ig)-bound proteins in ovarian cancer and of ovarian cancer cell surface MHC-II bound peptides also revealed a TP53-MYC related network of antigens. Our findings support the occurrence of a humoral immune response to antigens linked to ovarian cancer driver genes that may have utility for early detection applications.

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