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However, it remains uncertain whether these AAbs are specific to tumor\u2010associated antigens. In this study, we explored the IgG and IgM autoantibody repertoires in both the in\u00a0situ tissue microenvironment and peripheral blood as potential tumor\u2010specific biomarkers. We applied high\u2010density protein arrays to profile AAbs in the tumor\u2010infiltrating lymphocyte supernatants and corresponding serum from four patients with CRC, as well as in the serum of three noncancer controls. Our findings revealed that there were more reactive IgM AAbs than IgG in both the cell supernatant and corresponding serum, with a difference of approximately 3\u20135 times. Immunoglobulin G was predominant in the serum, while IgM was more abundant in the cell supernatant. We identified a range of AAbs present in both the supernatant and the corresponding serum, numbering between 432 and 780, with an average of 53.3% shared. Only 4.7% (<jats:italic>n<\/jats:italic>\u2009=\u200923) and 0.2% (<jats:italic>n<\/jats:italic>\u2009=\u20092) of reactive antigens for IgG and IgM AAbs, respectively, were specific to CRC. Ultimately, we compiled a list of 19 IgG AAb targets as potential tumor\u2010specific AAb candidates. Autoantibodies against one of the top candidates, p15INK4b\u2010related sequence\/regulation of nuclear pre\u2010mRNA domain\u2010containing protein 1A (RPRD1A), were significantly elevated in 53 CRC patients compared to 119 controls (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). The project revealed that tissue\u2010derived IgG AAbs, rather than IgM, are the primary source of tumor\u2010specific AAbs in peripheral blood. It also identified potential tumor\u2010specific AAbs that could be applied for noninvasive screening of CRC.<\/jats:p>","DOI":"10.1111\/cas.16011","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T22:47:16Z","timestamp":1700606836000},"page":"83-93","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Autoantibody repertoire profiling in tissue and blood identifies colorectal cancer\u2010specific biomarkers"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3242-8469","authenticated-orcid":false,"given":"Pei\u2010Fen","family":"Zhang","sequence":"first","affiliation":[{"name":"Affiliated Tumor Hospital of Xinjiang Medical University  \u00dcr\u00fcmqi China"},{"name":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat\u2010sen University Cancer Center  Guangzhou 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