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The diagnostics of oncological diseases is the key factor to their successful treatment. The process of tumor development is often accompanied by the change of autoantibody repertoire that can serve as a diagnostic marker of the oncological process but is rarely used in clinical practice. Apparently, most autoantibodies result from various nonspecific cellular and tissue changes which are caused by the tumor growth or other pathologic processes. We are developing an approach to search for autoantibody biomarkers produced in response to the activation of a few key oncogenes. This approach is based on the comparative immunoproteomic analysis including Difference gel electrophoresis (DIGE) followed by Westernblot analysis and tandem massspectrometry identification of the detected antigenic targets. To search for the thyroid cancer autoantigens we sequentially compared the proteome of normal cells of human thyroid follicular epithelium (Nthyori 31) with the proteomes of three variants of this cell line stably transfected by lentiviral constructs expressing the key oncogenes of thyroid cancer, BRAF(V600E), NRAS(Q61R) or chimeric protein СCDC6RET. In order to determine the autoantigens we estimated the ability of the differentially expressed proteins to react with sera of the cancer patients expressing the respective oncogenes, in comparison to sera from cancerfree controls. Our preliminary results suggest that it may be possible to detect antibodies to specific oncogeneinduced autoantigens produced by the tumor tissue. This work is supported by grant 161510423 from Russian Science Foundation