<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">zdor</journal-id><journal-title-group><journal-title xml:lang="ru">Проблемы здоровья и экологии</journal-title><trans-title-group xml:lang="en"><trans-title>Health and Ecology Issues</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2220-0967</issn><issn pub-type="epub">2708-6011</issn><publisher><publisher-name>Gomel State Medical University</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.51523/2708-6011.2018-15-4-20</article-id><article-id custom-type="elpub" pub-id-type="custom">zdor-85</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>НОВЫЕ ТЕХНОЛОГИИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>NEW TECHNOLOGIES</subject></subj-group></article-categories><title-group><article-title>СРАВНИТЕЛЬНЫЙ АНАЛИЗ МЕТИЛИРОВАНИЯ ГЕНОВ, АССОЦИИРОВАННЫХ С ОНКОПАТОЛОГИЕЙ МОЛОЧНОЙ ЖЕЛЕЗЫ И ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ, И ДИАГНОСТИЧЕСКИЕ ВОЗМОЖНОСТИ МЕТОДА НА ЕГО ОСНОВЕ</article-title><trans-title-group xml:lang="en"><trans-title>Comparative Analysis of Methylation of Genes Associated with Breast Cancer and Prostate Cancer, and the Diagnostic Potential of the Method on its Basis</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мартинков</surname><given-names>В. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Martinkov</surname><given-names>V. N.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Государственное учреждение «Республиканский научно-практический центр радиационной медицины и экологии человека»</institution></aff><aff xml:lang="en"><institution>State institution "Republican Scientific and Practical Center Radiation Medicine and Human Ecology "</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2018</year></pub-date><pub-date pub-type="epub"><day>28</day><month>12</month><year>2018</year></pub-date><volume>0</volume><issue>4</issue><fpage>103</fpage><lpage>109</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Мартинков В.Н., 2018</copyright-statement><copyright-year>2018</copyright-year><copyright-holder xml:lang="ru">Мартинков В.Н.</copyright-holder><copyright-holder xml:lang="en">Martinkov V.N.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://journal.gsmu.by/jour/article/view/85">https://journal.gsmu.by/jour/article/view/85</self-uri><abstract><p>Цель: сопоставить частоты метилирования девяти генов при раке предстательной железы (РПЖ) и раке молочной железы (РМЖ) и выделить единую панель генов, перспективную для использования в качестве дополнительного маркера при диагностике данных форм рака. Материалы и методы. Анализ метилирования промоторных областей девяти генов ( RARβ, HIN1, DAPK, RASSF1A, GSTP1, CCND2, p16, APC и hMLH1 ) выполнен посредством метилспецифической полимеразной цепной реакции с электрофоретической детекцией. Результаты. Определены и сопоставлены частоты метилирования девяти генов в биопсийном материале 68 пациентов с РПЖ, 39 пациентов с доброкачественной гиперплазией предстательной железы/простатической интраэпителиальной неоплазией (ДГПЖ/ПИН), операционном материале 104 пациенток с РМЖ и 38 пациенток с доброкачественными узловыми образованиями молочной железы (ДУОМЖ) (фиброаденома, узловая мастопатия). Заключение. Установлено, что в образцах злокачественной опухолевой ткани по сравнению с таковой в образцах с доброкачественной патологией как среди пациентов с заболеваниями предстательной железы, так и среди пациенток с патологией молочной железы статистически значимо чаще выявляется метилирование пяти генов ( RARβ, HIN1, CCND2, APC и GSTP1) из девяти проанализированных. В опухолевой ткани пациентов с РПЖ частота метилирования каждого из указанных пяти генов значимо больше в сравнении с пациентками с РМЖ. Метилирование двух или более генов из пяти при РПЖ определялось в 89,7 % случаев, при ДГПЖ/ПИН - в 23,1 %, что в 3,9 раза меньше, ОШ - 29,1 (95 % ДИ [9,9-85,6]), p &lt; 0,001. Диагностическая чувствительность метода составила 89,7 % при специфичности 76,9 % и точности 85 %. Метилирование одного или более генов из пяти в группе пациенток с РМЖ определялось в 80,8 % случаев, при ДУОМЖ - в 13,2 %, что в 6,1 раза меньше, ОШ - 27,7 (95 % ДИ [9,6-80,0]), p &lt; 0,001. Соответственно, чувствительность метода была равна 80,8 %, специфичность - 86,8 % и точность - 82,4 %.</p></abstract><trans-abstract xml:lang="en"><p>Objective: to compare the methylation rates of nine genes in prostate cancer and breast cancer and to identify a single panel of genes that is promising for its use as an additional marker in the diagnosis of these types of cancer. Material and methods. The methylation analysis of promoter areas of 9 genes ( RARβ , HIN1 , DAPK , RASSF1A , GSTP1 , CCND2 , p16 , APC and hMLH1 ) was performed by means of methylspecific polymerase chain reaction with electrophoretic detection. Results. We have identified and compared the methylation rates of the 9 genes in the biopsy material of 68 patients with prostate cancer, 39 patients with benign prostatic hyperplasia / prostatic intraepithelial neoplasia (BPH/PIN), surgical material from 104 female patients with breast cancer and 38 patients with benign tumors of the mammary gland (fibroadenoma, nodal mastopathy). Conclusion. It has been found that methylation of five genes ( RARβ , HIN1 , CCND2 , APC and GSTP1 ) out of the nine analyzed genes is statistically significantly more common in samples of malignant tumor tissue compared to that in samples with benign pathology both among patients with prostate diseases and among patients with breast pathology. The methylation rate of each of these five genes is significantly higher in the tumor tissue of patients with prostate cancer compared to those with breast cancer. Methylation of two or more genes out of five in prostate cancer was detected in 89.7 % of cases, in BPH / PIN - in 23.1 %, which is 3.9 times as little, OR - 29.1 (95 % CI [9.9-85, 6]), p &lt; 0.001. The diagnostic sensitivity of the method was 89.7 % with specificity of 76.9 % and accuracy of 85.0 %. Methylation of one or more genes out of five in the group of patients with breast cancer was detected in 80.8 % cases, with benign tumors of the mammary gland in 13.2 % cases, which is 6.1 times as little, OR - 27.7 (95 % CI [9.6-80.0]), p &lt; 0.001. Accordingly, the sensitivity of the method was equal to 80.8 %, specificity - 86.8 %, and accuracy - 82.4 %.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>рак молочной железы</kwd><kwd>рак предстательной железы</kwd><kwd>метелирование ДНК</kwd></kwd-group><kwd-group xml:lang="en"><kwd>breast cancer</kwd><kwd>prostate cancer</kwd><kwd>DNA methylation</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Delpu Y, Cordelier P, Cho WC, Torrisani J. DNA methylation and cancer diagnosis. Int J Mol Sci. 2013;14(7):15029-58. doi: 10.3390/ijms140715029.</mixed-citation><mixed-citation xml:lang="en">Delpu Y, Cordelier P, Cho WC, Torrisani J. DNA methylation and cancer diagnosis. Int J Mol Sci. 2013;14(7):15029-58. doi: 10.3390/ijms140715029.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Perry AS, Foley R, Woodson K, Lawler M. The emerging roles of DNA methylation in the clinical management of prostate cancer. Endocr Relat Cancer. 2006;13(2):357-77. doi: 10.1677/erc.1.01184.</mixed-citation><mixed-citation xml:lang="en">Perry AS, Foley R, Woodson K, Lawler M. The emerging roles of DNA methylation in the clinical management of prostate cancer. Endocr Relat Cancer. 2006;13(2):357-77. doi: 10.1677/erc.1.01184.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Bastian PJ, Ellinger J, Wellmann A, Wernert N, Heukamp LC, Müller SC, et al. Diagnostic and prognostic information in prostate cancer with the help of a small set of hypermethylated gene loci. Clin Cancer Res. 2005;11(11):4097-106. doi: 10.1158/1078-0432.CCR-04-1832.</mixed-citation><mixed-citation xml:lang="en">Bastian PJ, Ellinger J, Wellmann A, Wernert N, Heukamp LC, Müller SC, et al. Diagnostic and prognostic information in prostate cancer with the help of a small set of hypermethylated gene loci. Clin Cancer Res. 2005;11(11):4097-106. doi: 10.1158/1078-0432.CCR-04-1832.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Long MD, Smiraglia DJ, Campbell MJ. The genomic impact of DNA CpG methylation on gene expression; relationships in prostate cancer. Biomolecules. 2017 Feb 14;7(1):1-20. doi: 10.3390/biom7010015.</mixed-citation><mixed-citation xml:lang="en">Long MD, Smiraglia DJ, Campbell MJ. The genomic impact of DNA CpG methylation on gene expression; relationships in prostate cancer. Biomolecules. 2017 Feb 14;7(1):1-20. doi: 10.3390/biom7010015.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Jovanovic J, Rønneberg JA, Tost J, Kristensen V. The epigenetics of breast cancer. Mol Oncol. 2010;4(3):242-54. doi: 10.1016/j.molonc.2010.04.002.</mixed-citation><mixed-citation xml:lang="en">Jovanovic J, Rønneberg JA, Tost J, Kristensen V. The epigenetics of breast cancer. Mol Oncol. 2010;4(3):242-54. doi: 10.1016/j.molonc.2010.04.002.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Xu J, Shetty PB, Feng W, Chenault C, Bast RC, Issa J-PJ, et al. Methylation of HIN-1, RASSF1A, RIL and CDH13 in breast cancer is associated with clinical characteristics, but only RASSF1A methylation is associated with outcome. BMC Cancer. 2012;12:243. doi: 10.1186/1471-2407-12-243.</mixed-citation><mixed-citation xml:lang="en">Xu J, Shetty PB, Feng W, Chenault C, Bast RC, Issa J-PJ, et al. Methylation of HIN-1, RASSF1A, RIL and CDH13 in breast cancer is associated with clinical characteristics, but only RASSF1A methylation is associated with outcome. BMC Cancer. 2012;12:243. doi: 10.1186/1471-2407-12-243.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Hoque MO, Feng Q, Toure P, Dem A, Critchlow CW, Hawes SE, et al. Detection of aberrant methylation of four genes in plasma DNA for the detection of breast cancer. J Clin Oncol. 2006;24(26):4262-69. doi: 10.1200/JCO.2005.01.3516.</mixed-citation><mixed-citation xml:lang="en">Hoque MO, Feng Q, Toure P, Dem A, Critchlow CW, Hawes SE, et al. Detection of aberrant methylation of four genes in plasma DNA for the detection of breast cancer. J Clin Oncol. 2006;24(26):4262-69. doi: 10.1200/JCO.2005.01.3516.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Rouprêt M, Hupertan V, Yates DR, Catto JWF, Rehman I, Meuth M, et al. Molecular detection of localized prostate cancer using quantitative methylation-specific PCR on urinary cells obtained following prostate massage. Clin Cancer Res. 2007;13(6):1720-25. doi: 10.1158/1078-0432.CCR-06-2467.</mixed-citation><mixed-citation xml:lang="en">Rouprêt M, Hupertan V, Yates DR, Catto JWF, Rehman I, Meuth M, et al. Molecular detection of localized prostate cancer using quantitative methylation-specific PCR on urinary cells obtained following prostate massage. Clin Cancer Res. 2007;13(6):1720-25. doi: 10.1158/1078-0432.CCR-06-2467.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Van Neste L, Partin AW, Stewart GD, Epstein JI, Harrison DJ, Van Criekinge W. Risk score predicts high-grade prostate cancer in DNA-methylation positive, histopathologically negative biopsies. Prostate. 2016;76(12):1078-87. doi: 10.1002/pros.23191.</mixed-citation><mixed-citation xml:lang="en">Van Neste L, Partin AW, Stewart GD, Epstein JI, Harrison DJ, Van Criekinge W. Risk score predicts high-grade prostate cancer in DNA-methylation positive, histopathologically negative biopsies. Prostate. 2016;76(12):1078-87. doi: 10.1002/pros.23191.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Zhao F, Olkhov-Mitsel E, van der Kwast T, Sykes J, Zdravic D, Venkateswaran V, et al. Urinary DNA methylation biomarkers for non-invasive prediction of aggressive disease in patients with prostate cancer on Active Surveillance. J Urol. 2017;197(2):335-41. doi: 10.1016/j.juro.2016.08.081.</mixed-citation><mixed-citation xml:lang="en">Zhao F, Olkhov-Mitsel E, van der Kwast T, Sykes J, Zdravic D, Venkateswaran V, et al. Urinary DNA methylation biomarkers for non-invasive prediction of aggressive disease in patients with prostate cancer on Active Surveillance. J Urol. 2017;197(2):335-41. doi: 10.1016/j.juro.2016.08.081.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Hoque MO, Feng Q, Toure P, Dem A, Critchlow CW, Hawes SE, et al. Detection of aberrant methylation of four genes in plasma DNA for the detection of breast cancer. J Clin Oncol. 2006;24(26):4262-69. doi: 10.1200/JCO.2005.01.3516.</mixed-citation><mixed-citation xml:lang="en">Hoque MO, Feng Q, Toure P, Dem A, Critchlow CW, Hawes SE, et al. Detection of aberrant methylation of four genes in plasma DNA for the detection of breast cancer. J Clin Oncol. 2006;24(26):4262-69. doi: 10.1200/JCO.2005.01.3516.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Tao MH, Shields PG, Nie J, Millen A, Ambrosone CB, Edge SB, et al. DNA hypermethylation and clinicopathological features in breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study. Breast Cancer Res Treat. 2009;114(3):559-68. doi: 10.1007/s10549-008-0028-z.</mixed-citation><mixed-citation xml:lang="en">Tao MH, Shields PG, Nie J, Millen A, Ambrosone CB, Edge SB, et al. DNA hypermethylation and clinicopathological features in breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study. Breast Cancer Res Treat. 2009;114(3):559-68. doi: 10.1007/s10549-008-0028-z.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Strand SH, Orntoft TF, Sorensen KD. Prognostic DNA methylation markers for prostate cancer. Int J Mol Sci. 2014;15(9):16544-76. doi: 10.3390/ijms150916544.</mixed-citation><mixed-citation xml:lang="en">Strand SH, Orntoft TF, Sorensen KD. Prognostic DNA methylation markers for prostate cancer. Int J Mol Sci. 2014;15(9):16544-76. doi: 10.3390/ijms150916544.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Силин АЕ, Мартинков ВН, Надыров ЭА, Пестриков ЕВ, Либуркин ОМ, Задорожнюк АА, и др. Сравнительный анализ статуса метилирования 11 генов-супрессоров в ткани предстательной железы пациентов с доброкачественной патологией, раком предстательной железы и лиц без патологии. Проблемы Здоровья и Экологии. 2012;4:92-8.</mixed-citation><mixed-citation xml:lang="en">Силин АЕ, Мартинков ВН, Надыров ЭА, Пестриков ЕВ, Либуркин ОМ, Задорожнюк АА, и др. Сравнительный анализ статуса метилирования 11 генов-супрессоров в ткани предстательной железы пациентов с доброкачественной патологией, раком предстательной железы и лиц без патологии. Проблемы Здоровья и Экологии. 2012;4:92-8.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Силин АЕ, Мартинков ВН, Надыров ЭА, Мартыненко СМ, Родько ДБ. Частоты гиперметилирования промоторных областей генов-супрессоров при раке молочной железы. Мед-Биол Проблемы Жизнедеятельности. 2010;1:56-63.</mixed-citation><mixed-citation xml:lang="en">Силин АЕ, Мартинков ВН, Надыров ЭА, Мартыненко СМ, Родько ДБ. Частоты гиперметилирования промоторных областей генов-супрессоров при раке молочной железы. Мед-Биол Проблемы Жизнедеятельности. 2010;1:56-63.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
