ИСТИНА

Background. Renal cell carcinoma (RCC) is the second most common cancer among uronephrological cancers that characterizes as highly aggressive and invasive with high frequency of metastasis [1]. RCC is also lack in specific symptoms, therefore it is difficult to detect and it is usually diagnosed at late stage of disease in routine screening or during examinations for another pathology. Methods of early specific RCC diagnostic are poorly developed. Recent advances in diagnostic biomarkers of RCC are based on detection of tumor-associated antigens (TAAs) or nucleic acids in blood flow or in tumor itself. However, tumor heterogeneity and complexity of the biopsy procedure may be limiting factors. Contrariwise, blood is less invasive to obtain, but biomarkers undergo degradation by circulating nucleases and proteases, thereby their signals is damped in blood assays [2]. Another type of biomarkers that could be applied for RCC diagnosis is autoantibodies against aberrantly expressed proteins. In contrast to TAAs and nucleic acids, antibodies are far more stable in blood and antibody response is early and enduring [3]. The basis for antibody response against tumor is aberrant expression of TAAs by that tumor. Several TAAs were proposed to be aberrantly expressed in RCC and cancer-retinal proteins are one of that group of proteins. In this study, we analyzed whether aberrant expression of cancer-retinal protein visual arrestin can be detected in RCC and whether autoantibodies against visual arrestin will be produces. Materials and methods. Immunohistochemistry was used to assess the presence of visual arrestin in primary tumors and metastases of 39 patients with RCC and renal oncocytoma. Bisulfite sequencing was employed to analyse the methylation status of the promoter of the SAG gene encoding visual arrestin. Western blot analysis was performed to detect autoantibodies against visual arrestin in serum samples of 33 RCC patients. Results. Visual arrestin was found to be expressed in RCC and renal oncocytoma cells in 58.7% and 90% of cases, respectively. Hypomethylation of the SAG gene promoter is unlikely to be the mechanism for the aberrant expression of visual arrestin. Autoantibodies against visual arrestin were detected in sera of 75% of RCC patients.   Conclusion. Expression of visual arrestin can be detected frequently in different malignant renal tumor cells. Moreover, it was found that RCC patients often produce autoantibodies against aberrantly expressed visual arrestin. Taking in account such findings and advantages of antibodies over TAAs and nucleic acids as biomarkers, autoantibody against visual arrestin proposed as a potential biomarker of RCC.