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Tumor Biology

, Volume 37, Issue 7, pp 9899–9907 | Cite as

The cancer-retina antigen recoverin as a potential biomarker for renal tumors

  • Marina O. Golovastova
  • Larisa V. Tsoy
  • Anna V. Bocharnikova
  • Dmitry O. Korolev
  • Olga S. Gancharova
  • Ekaterina A. Alekseeva
  • Ekaterina B. Kuznetsova
  • Lyudmila V. Savvateeva
  • Elena E. Skorikova
  • Vladimir V. Strelnikov
  • Vladimir A. Varshavsky
  • Andrey Z. Vinarov
  • Vladimir N. Nikolenko
  • Peter V. Glybochko
  • Evgeni Yu. Zernii
  • Andrey A. ZamyatninJr.
  • Alexandr V. Bazhin
  • Pavel P. Philippov
Original Article

Abstract

The renal cell carcinoma is the ninth most common cancer with an increasing occurrence and mortality. Recoverin is the first retina-specific photoreceptor protein that was shown to undergo aberrant expression, due to its promoter demethylation, as a cancer-retina antigen in a number of malignant tumors. In this work, we demonstrated that recoverin is indeed expressed in 68.4 % of patients with different subtypes of renal cell carcinoma, and this expression has tendency to correlate with tumor size. Interestingly, 91.7 % of patients with the benign renal tumor, oncocytoma, express recoverin as well in their tumor. Epigenetic analysis of the recoverin gene promoter revealed a stable mosaic methylation pattern with the predominance of the methylated state, with the exception of -80 and 56 CpG dinucleotides (CpGs). While the recoverin expression does not correlate withoverall survival of the tumor patients, the methylation of the recoverin gene promoter at -80 position is associated with better overall survival of the patients. This work is the first report pointing towards the association of overall survival of renal cell carcinoma (RCC) patients with promoter methylation of a cancer-retina antigen. Taken together, these data allow to consider recoverin as a potential therapeutic target and/or marker for renal tumors.

Keywords

Recoverin Cancer-retina antigens Onconeural antigens DNA methylation Renal cancer 

Abbreviations

AAR

autoantibodies against recoverin

CTA

cancer-testis (germline) antigens

CpGs

CpG dinucleotides

PNA

paraneoplastic antigen

TA

tumor antigen

TSS

transcription start site

Notes

Acknowledgments

We are indebted to Ms. E.V. Bragina for her help in the preparation of the manuscript. This work was supported in part by grant numbers 12-04-00922 and 15-04-05171 to PPPh, 14-04-32360 to LVS, 15-04-07963 to EYZ, and 16-54-53115 to AAZ from the Russian Foundation for Basic Research.

Compliance with ethical standards

All experiments reported in this study involving human subjects complied with the ethical standards of the committee responsible for human experimentation (institutional and national) and with the Helsinki Declaration of 1975 as revised in 2008 and approved by the Ethics Committee at Sechenov First Moscow State Medical University (N04-12) prior to this study.

Informed consent

Informed consent was obtained from all patients included in the study.

Conflicts of interest

None

Supplementary material

13277_2016_4885_MOESM1_ESM.doc (36 kb)
Supplementary Table 1 Bisulfite sequencing primers and their genomic locations, PCR conditions and amplicon lengths. (DOC 35 kb)
13277_2016_4885_MOESM2_ESM.doc (30 kb)
Supplementary Fig. 1 Schematic representation of the first exon and promoter region of the recoverin gene. (DOC 30 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Marina O. Golovastova
    • 1
  • Larisa V. Tsoy
    • 2
  • Anna V. Bocharnikova
    • 3
  • Dmitry O. Korolev
    • 4
  • Olga S. Gancharova
    • 1
  • Ekaterina A. Alekseeva
    • 3
    • 5
  • Ekaterina B. Kuznetsova
    • 3
    • 5
  • Lyudmila V. Savvateeva
    • 3
  • Elena E. Skorikova
    • 1
  • Vladimir V. Strelnikov
    • 3
    • 5
    • 6
  • Vladimir A. Varshavsky
    • 2
  • Andrey Z. Vinarov
    • 4
  • Vladimir N. Nikolenko
    • 7
    • 8
  • Peter V. Glybochko
    • 4
  • Evgeni Yu. Zernii
    • 1
  • Andrey A. ZamyatninJr.
    • 1
    • 3
  • Alexandr V. Bazhin
    • 9
  • Pavel P. Philippov
    • 1
  1. 1.Department of Cell Signalling, Belozersky Institute of Physico-Chemical BiologyLomonosov Moscow State UniversityMoscowRussia
  2. 2.Anatomic Pathology DepartmentSechenov First Moscow State Medical UniversityMoscowRussia
  3. 3.Institute of Molecular MedicineSechenov First Moscow State Medical UniversityMoscowRussia
  4. 4.Institute of Uronephrology and Human Reproductive HealthSechenov First Moscow State Medical UniversityMoscowRussia
  5. 5.Research Centre for Medical GeneticsMoscowRussia
  6. 6.Medical Biology Faculty, Department of Molecular Genetics and CytogeneticsPirogov Russian National Research Medical UniversityMoscowRussia
  7. 7.Sechenov First Moscow State Medical UniversityMoscowRussia
  8. 8.Faculty of Basic MedicineLomonosov Moscow State UniversityMoscowRussia
  9. 9.Department of General, Visceral, and Transplant SurgeryLudwig-Maximilians-University MunichMunichGermany

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