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Non-Invasive Diagnostics of Renal Cell Carcinoma Using Ultrasensitive Immunodetection of Cancer-Retina Antigens

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Abstract

Renal cell carcinoma (RCC) is the most common urological malignancy with a high mortality and low detection rate. One of the approaches to improving its diagnostics may be the search for new non-invasive biomarkers in liquid biopsy and development of more sensitive methods for their detection. Cancer-retina antigens, which are known to be aberrantly expressed in malignant tumors, are present in liquid biopsy at extremely low concentrations. Using the developed multiplex immunoassay with a detection limit of 0.1 pg/ml, urine and serum samples of 89 patients with RCC and 50 non-cancer patients were examined for the presence of cancer-retina antigens (arrestin, recoverin, rhodopsin kinase, and transducin); the difference between the RCC and control groups was evaluated with the χ2 test. The results showed high diagnostic efficiency of a combination of arrestin and recoverin: at a threshold of 0.1 pg/ml, the sensitivity was 96%, specificity 92%, and AUC = 0.96 (95% confidence interval, 0.93-0.99). Seven days after nephrectomy, the concentration of the antigens returned to the level characteristic of the control group. Therefore, arrestin in a combination with recoverin can serve as a diagnostic non-invasive urinary biomarker of RCC.

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Abbreviations

AUC:

area under the curve

CI:

confidence interval

CAIX:

carbonic anhydrase IX

RCC:

renal cell carcinoma

RKIP:

Raf kinase inhibitor protein

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Funding

This work was supported by the Russian Foundation for Basic Research (project no. 19-75-10025).

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Authors and Affiliations

  1. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Russia

    Yuri M. Shlyapnikov, Ekaterina A. Malakhova & Elena A. Shlyapnikova

  2. Institute for Urology and Reproductive Health, Sechenov First Moscow State Medical University, 119991, Moscow, Russia

    Natalia V. Potoldykova, Yana A. Svetocheva & Andrei Z. Vinarov

  3. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Pushchino, Moscow Region, Russia

    Dmitry V. Zinchenko

  4. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991, Moscow, Russia

    Evgeni Yu. Zernii & Andrey A. Zamyatnin Jr.

  5. Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991, Moscow, Russia

    Andrey A. Zamyatnin Jr.

  6. Department of Biotechnology, Sirius University of Science and Technology, 354340, Sochi, Russia

    Andrey A. Zamyatnin Jr.

  7. Faculty of Health and Medical Sciences, University of Surrey, GU2 7XH, Guildford, Surrey, UK

    Andrey A. Zamyatnin Jr.

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  1. Yuri M. Shlyapnikov
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  2. Ekaterina A. Malakhova
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  3. Natalia V. Potoldykova
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  6. Dmitry V. Zinchenko
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Correspondence to Yuri M. Shlyapnikov.

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Shlyapnikov, Y.M., Malakhova, E.A., Potoldykova, N.V. et al. Non-Invasive Diagnostics of Renal Cell Carcinoma Using Ultrasensitive Immunodetection of Cancer-Retina Antigens. Biochemistry Moscow 87, 658–666 (2022). https://doi.org/10.1134/S0006297922070070

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