Hypermethylation of a group of microRNA genes in primary tumors and peritoneal metastases of ovarian cancer

  • A. M. Burdennyy Institute of General Pathology and Pathophysiology, Baltiyskaya Str. 8, Moscow 125315, Russia http://orcid.org/0000-0002-9398-8075
  • D. O. Utkin N.N. Blokhin National Medical Research Center of Oncology, Kashirskoe Shosse 24, Moscow 115478, Russia http://orcid.org/0000-0002-6620-2073
  • E. A. Filippova Institute of General Pathology and Pathophysiology, Baltiyskaya Str. 8, Moscow 125315, Russia http://orcid.org/0000-0001-7172-0433
  • V. I. Loginov Institute of General Pathology and Pathophysiology, Baltiyskaya Str. 8, Moscow 125315, Russia; Research Center of Medical Genetics, Moskvorechje 1, Moscow 115478, Russia http://orcid.org/0000-0002-0423-7801
  • I. V. Pronina Institute of General Pathology and Pathophysiology, Baltiyskaya Str. 8, Moscow 125315, Russia http://orcid.org/0000-0003-2668-8096
  • M. V. Fridman N.I. Vavilov Institute of General Genetics, Gubkina Str. 3, Moscow 119333, Russia
  • T. P. Kazubskaya N.N. Blokhin National Medical Research Center of Oncology, Kashirskoe Shosse 24, Moscow 115478, Russia http://orcid.org/0000-0001-5856-0017
  • N. E. Kuslinskii N.N. Blokhin National Medical Research Center of Oncology, Kashirskoe Shosse 24, Moscow 115478, Russia
  • Eleonora A. Braga Institute of General Pathology and Pathophysiology, Baltiyskaya Str. 8, Moscow 125315, Russia; Research Center of Medical Genetics, Moskvorechje 1, Moscow 115478, Russia
DOI: https://doi.org/10.25557/0031-2991.2018.04.58-66
Keywords: ovarian cancer, microRNA, genes, hypermethylation, peritoneal metastasis, primary tumors, macro-metastases

Abstract

Ovarian cancer is characterized by the early metastatic activity and high frequency of poor prognosis. Earlier we described a group of miRNA genes where methylation is involved in the development and progression of ovarian cancer. Aim. To expand the array of miRNA genes hypermethylated in ovarian cancer and to study their correlation with metastatic activity both in primary tumors and macro-metastases. Methods. For our study, we used DNA bisulfite conversion followed by methyl-specific PCR. Results. A significant increase in methylation frequency was observed in 54 samples of ovarian cancer compared with histologically intact ovarian tissue for 6 of 7 studied miRNA genes, MIR-107, MIR-1258, MIR-130b, MIR-34b/c, MIR-9-1, and MIR-9-3 (p<10-3, FDR = 0.01). Five miRNA genes statistically significantly correlated with cancer progression, particularly with the metastatic activity. When comparing the methylation status of tumor samples from 37 non-metastatic and 17 metastatic patients we found statistically significant correlations with metastasis for MIR-1258 (p≤0.04), MIR-130b (p≤0.01), and MIR-34b/c (p≤0.001), and tendencies for MIR-9-1 and MIR-9-3. Analysis of primary tumors and matched peritoneal metastases in 13 patients confirmed the association between methylation and metastasis for these 5 genes. Conclusion. This study demonstrated a systemic role of hypermethylation for the group of miRNA genes in peritoneal metastasis in patients with ovarian cancer.

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Published
2018-11-21
How to Cite
Burdennyy A. M., Utkin D. O., Filippova E. A., Loginov V. I., Pronina I. V., Fridman M. V., Kazubskaya T. P., Kuslinskii N. E., Braga E. A. Hypermethylation of a group of microRNA genes in primary tumors and peritoneal metastases of ovarian cancer // Patologicheskaya Fiziologiya i Eksperimental’naya Terapiya (Pathological physiology and experimental therapy). 2018. VOL. 62. № 4. PP. 58–66.
Issue
Vol. 62 No. 4 (2018)
Section
Original research

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