System of Markers Based on the Methylation of a Group of Proapoptotic Genes in Combination with MicroRNA in the Diagnosis of Breast Cancer
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Systems of markers for the diagnosis of breast cancer based on DNA methylation of a group of suppressor protein-coding genes, hypermethylated microRNA genes, and their combinations were compiled. On a representative sample of 70 paired breast cancer specimens (tumor/normal), MS-PCR analysis revealed a significant increase in the methylation frequency of 5 protein-coding genes: RASSF1A suppressor and apoptosis genes APAF1, BAX, BIM/BCL2L11, and DAPK1 (34-61% vs. 4-24%) and 6 microRNA genes: MIRG124G1, MIRG125bG1, MIRG129G2, MIRG148a, MIRG34b/c, and MIRG9G3 (36-76% vs. 6-27%). ROC-analysis showed that a combination of 4 genes (APAF1, BAX, BIM/BCL2L11, and DAPK1) and MIRG125bG1 gene constitute a highly efficient 5-marker system with 100% specificity and sensitivity of 94-96% at AUC=0.98-0.97, suitable also for patients with stage I and II breast cancer. Detection of methylation of at least one gene in this system in biopsy or postoperative material is sufficient to refer the sample to breast cancer.
Key Wordsproapoptotic genes microRNAs methylation breast cancer diagnostic marker systems
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- 1.Braga EA, Loginov VI, Filippova EA, Burdennyi AM, Pronina IV, Kazubskaya TP, Khodyrev DS, Utkin DO, Kushlinskii DN, Adamyan LV, Kushlinskii NE. Diagnostic Value of a Group of MicroRNA Genes Hypermethylated in Ovarian Carcinoma. Bull. Exp. Biol. Med. 2018;166(2):253-256. doi: https://doi.org/10.1007/s10517-018-4326-0 CrossRefPubMedGoogle Scholar
- 2.Malignant Neoplasms in Russia for 2017 (Morbidity and Mortality). Kaprin AD, Starinskii VV, Petrova GV, eds. Moscow, 2018. Russian.Google Scholar
- 4.Loginov VI, Pronina IV, Burdennyi AM, Pereyaslova EA, Braga EA, Kazubskaya TP, Kushlinskii NE. Role of Methylation in the Regulation of Apoptosis Genes APAF1, DAPK1, and BCL2 in BC. Bull. Exp. Biol. Med. 2017;162(6):797-800. doi: https://doi.org/10.1007/s10517-017-3716-z CrossRefPubMedGoogle Scholar
- 7.Alvarez MC, Maso V, Torello CO, Ferro KP, Saad STO. The polyphenol quercetin induces cell death in leukemia by targeting epigenetic regulators of pro-apoptotic genes. Clin. Epigenetics. 2018;10(1). ID 139. doi: https://doi.org/10.1186/s13148-018-0563-3
- 11.Kurman RJ, Carcangiu ML, Herrington CS, Young RH. WHO classification of tumours of female reproductive organs. Lyon, 2014.Google Scholar
- 12.Pronina IV, Loginov VI, Burdennyy AM, Fridman MV, Kazubskaya TP, Dmitriev AA, Braga EA. Expression and DNA methylation alterations of seven cancer-associated 3p genes and their predicted regulator miRNAs (miR-129-2, miR-9-1) in breast and ovarian cancers. Gene. 2016;576(1, Pt 3):483-491.CrossRefGoogle Scholar