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Baldin, Alexey; Grishina, Alena N.; Korolev, Dmitry O.; Kuznetsova, Ekaterina B.; Golovastova, Marina O.; Kalpinskiy, Alexey S.; Alekseev, Boris Y.; Kaprin, Andrey D.; Zinchenko, Dmitry; Savvateeva, Lyudmila; Varshaysky, Vladimir A.; Zernii, Evgeni Yu; Vinarov, Andrey Z.; Bazhin, Alexandr; Philippov, Pavel P.; Zamyatnin, Andrey A. (2019): Autoantibody against arrestin-1 as a potential biomarker of renal cell carcinoma. In: Biochimie, Vol. 157: pp. 26-37
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Abstract

Renal cell carcinoma (RCC) is the second-most common uronephrological cancer. In the absence of specific symptoms, early diagnosis of RCC is challenging. Monitoring of the aberrant expression of tumour-associated antigens (TAAs) and related autoantibody response is considered as a novel approach of RCC diagnostics. The aim of this study was to examine the aberrant expression of arrestin-1 in renal tumours, to investigate the possible epigenetic mechanism underlying arrestin-1 expression, and to assess the frequency of anti-arrestin-1 autoantibody response. Immunohistochemistry was used to assess the presence of arrestin-1 in primary tumours 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 arrestin-1. Western blot analysis was performed to detect autoantibodies against arrestin-1 in serum samples of 36 RCC and oncocytoma patients. Arrestin-1 was found to be expressed in RCC (58.7% of cases) and renal oncocytoma (90% of cases) cells, while being absent in healthy kidney. The expression of arrestin-1 in RCC metastases was more prominent than in primary tumours. Hypo-methylation of the SAG gene promoter is unlikely to be the mechanism for the aberrant expression of arrestin-1. Autoantibodies against arrestin-1 were detected in sera of 75% of RCC patients. Taken together, our findings suggest employment of autoantibody against arrestin-1 as biomarker of RCC. (C) 2018 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.