Autoantibody against arrestin-1 as a potential biomarker of renal cell carcinoma

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. Hypomethylation 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.

Biochimie. 2018 Oct 30 [Epub ahead of print]

Alexey V Baldin, Alena N Grishina, Dmitry O Korolev, Ekaterina B Kuznetsova, Marina O Golovastova, Alexey S Kalpinskiy, Boris Y Alekseev, Andrey D Kaprin, Dmitry V Zinchenko, Lyudmila V Savvateeva, Vladimir A Varshavsky, Evgeni Yu Zernii, Andrey Z Vinarov, Alexandr V Bazhin, Pavel P Philippov, Andrey A Zamyatnin

Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991, Moscow, Russia. Electronic address: ., Anatomic Pathology Department, Sechenov First Moscow State Medical University, 119991, Moscow, Russia. Electronic address: ., Institute of Uronephrology and Human Reproductive Health, Sechenov First Moscow State Medical University, 119991, Moscow, Russia., Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991, Moscow, Russia; Research Centre for Medical Genetics, 115522, Moscow, Russia. Electronic address: ., Department of Cell Signalling, Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991, Moscow, Russia., P.A. Hertzen Moscow Oncology Research Center, National Medical Research Center of Radiology, 125284, Moscow, Russia., P.A. Hertzen Moscow Oncology Research Center, National Medical Research Center of Radiology, 125284, Moscow, Russia. Electronic address: ., Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russia. Electronic address: ., Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991, Moscow, Russia., Anatomic Pathology Department, Sechenov First Moscow State Medical University, 119991, Moscow, Russia., Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991, Moscow, Russia; Department of Cell Signalling, Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991, Moscow, Russia., Institute of Uronephrology and Human Reproductive Health, Sechenov First Moscow State Medical University, 119991, Moscow, Russia. Electronic address: ., Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany. Electronic address: ., Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991, Moscow, Russia; Department of Cell Signalling, Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991, Moscow, Russia. Electronic address: .