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<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">oncotomsk</journal-id><journal-title-group><journal-title xml:lang="ru">Сибирский онкологический журнал</journal-title><trans-title-group xml:lang="en"><trans-title>Siberian journal of oncology</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1814-4861</issn><issn pub-type="epub">2312-3168</issn><publisher><publisher-name>Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.21294/1814-4861-2021-20-2-61-67</article-id><article-id custom-type="elpub" pub-id-type="custom">oncotomsk-1756</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>ЛАБОРАТОРНЫЕ И ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>LABORATORY AND EXPERIMENTAL STUDIES</subject></subj-group></article-categories><title-group><article-title>МУЛЬТИПЛЕКСНОЕ ОПРЕДЕЛЕНИЕ ОНКОМАРКЕРОВ НА РАЗНЫХ СТАДИЯХ КОЛОРЕКТАЛЬНОГО РАКА</article-title><trans-title-group xml:lang="en"><trans-title>MULTIPLEX DETECTION OF TUMOR MARKERS FOR DIFFERENT STAGES OF COLORECTAL CANCER</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5602-6136</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ахмалтдинова</surname><given-names>Л. Л.</given-names></name><name name-style="western" xml:lang="en"><surname>Akhmaltdinova</surname><given-names>L. L.</given-names></name></name-alternatives><bio xml:lang="ru"><p> кандидат медицинских наук, заведующая лабораторией коллективного пользования научно-исследовательского центра </p><p>SPIN-код: 9212-3265. Researcher ID (WOS): B-8152-2018. Author ID (Scopus): 56285614700</p><p> Казахстан, 100008, г. Караганда, ул. Гоголя, 40 </p></bio><bio xml:lang="en"><p> PhD, Head of Laboratory</p><p>Researcher ID (WOS): B-8152-2018. Author ID (Scopus): 56285614700 </p><p> 40, Gogolya Street, Karaganda, 100008, Kazakhstan </p></bio><email xlink:type="simple">ahmaltdinova@qmu.kz</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6777-6864</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сирота</surname><given-names>В. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Sirota</surname><given-names>V. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p> доктор медицинских наук, профессор кафедры онкологии</p><p>SPIN-код: 3667-1148 </p><p> Казахстан, 100008, г. Караганда, ул. Гоголя, 40 </p></bio><bio xml:lang="en"><p> MD, Professor, Oncology Department </p><p> 40, Gogolya Street, Karaganda, 100008, Kazakhstan </p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7221-5305</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Жумалиева</surname><given-names>В. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Zhumalieva</surname><given-names>V. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p> доктор медицинских наук, ассистент профессора кафедры онкологии и лучевой диагностики </p><p> Казахстан, 100008, г. Караганда, ул. Гоголя, 40 </p></bio><bio xml:lang="en"><p> MD, DSc, Department of Oncology and Diagnostic Imaging </p><p> 40, Gogolya Street, Karaganda, 100008, Kazakhstan </p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7173-3138</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кадырова</surname><given-names>И. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kadyrova</surname><given-names>I. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p> доктор медицинских наук, старший научный сотрудник лаборатории коллективного пользования</p><p>SPIN-код: 2038-2991</p><p> Казахстан, 100008, г. Караганда, ул. Гоголя, 40 </p></bio><bio xml:lang="en"><p> MD, DSc, Senior Researcher </p><p> 40, Gogolya Street, Karaganda, 100008, Kazakhstan </p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2280-2146</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бабенко</surname><given-names>Д. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Babenko</surname><given-names>D. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p> доктор медицинских наук, директор научно-исследовательского центра</p><p>SPIN-код: 3567-2768. Researcher ID (WOS): P-8052-2017</p><p> Казахстан, 100008, г. Караганда, ул. Гоголя, 40 </p></bio><bio xml:lang="en"><p> MD, PhD, Director of Research Center</p><p>Researcher ID (WOS): P-8052-2017 </p><p> 40, Gogolya Street, Karaganda, 100008, Kazakhstan </p></bio><email xlink:type="simple">streampost@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5492-0046</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Тауешева</surname><given-names>З. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Tauesheva</surname><given-names>Z. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p> кандидат медицинских наук, ассистент профессора кафедры внутренних болезней № 1</p><p>SPIN-код: 6282-5045</p><p> Казахстан, 100008, г. Караганда, ул. Гоголя, 40 </p></bio><bio xml:lang="en"><p> MD, PhD, Department of Internal Diseases </p><p> 40, Gogolya Street, Karaganda, 100008, Kazakhstan </p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6971-8764</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Тайжанова</surname><given-names>Д. Ж.</given-names></name><name name-style="western" xml:lang="en"><surname>Taizhanova</surname><given-names>D. Zh.</given-names></name></name-alternatives><bio xml:lang="ru"><p> доктор медицинских наук, профессор, заведующая кафедрой внутренних болезней № 1</p><p>SPIN-код: 6295-5540</p><p> Казахстан, 100008, г. Караганда, ул. Гоголя, 40 </p></bio><bio xml:lang="en"><p> MD, Professor, Head of Department of Internal Diseases </p><p> 40, Gogolya Street, Karaganda, 100008, Kazakhstan </p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9968-9404</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ибраева</surname><given-names>А. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Ibraeva</surname><given-names>A. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>стажер-исследователь научно-исследовательского центра</p><p> Казахстан, 100008, г. Караганда, ул. Гоголя, 40 </p></bio><bio xml:lang="en"><p> Researcher, Research Center </p><p> 40, Gogolya Street, Karaganda, 100008, Kazakhstan </p></bio><email xlink:type="simple">aigera.tokpanova@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9122-1279</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Авдиенко</surname><given-names>О. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Avdienko</surname><given-names>O. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p> младший научный сотрудник научно-исследовательского центра</p><p>SPIN-код: 8822-3237</p><p> Казахстан, 100008, г. Караганда, ул. Гоголя, 40 </p></bio><bio xml:lang="en"><p> Junior Researcher, Research Center </p><p> 40, Gogolya Street, Karaganda, 100008, Kazakhstan </p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>НАО «Медицинский университет Караганды»</institution><country>Казахстан</country></aff><aff xml:lang="en"><institution>Karaganda Medical University</institution><country>Kazakhstan</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2021</year></pub-date><pub-date pub-type="epub"><day>29</day><month>04</month><year>2021</year></pub-date><volume>20</volume><issue>2</issue><fpage>61</fpage><lpage>67</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Ахмалтдинова Л.Л., Сирота В.Б., Жумалиева В.А., Кадырова И.А., Бабенко Д.Б., Тауешева З.Б., Тайжанова Д.Ж., Ибраева А.С., Авдиенко О.В., 2021</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="ru">Ахмалтдинова Л.Л., Сирота В.Б., Жумалиева В.А., Кадырова И.А., Бабенко Д.Б., Тауешева З.Б., Тайжанова Д.Ж., Ибраева А.С., Авдиенко О.В.</copyright-holder><copyright-holder xml:lang="en">Akhmaltdinova L.L., Sirota V.B., Zhumalieva V.A., Kadyrova I.A., Babenko D.B., Tauesheva Z.B., Taizhanova D.Z., Ibraeva A.S., Avdienko O.V.</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://www.siboncoj.ru/jour/article/view/1756">https://www.siboncoj.ru/jour/article/view/1756</self-uri><abstract><sec><title> Введение</title><p> Введение. Колоректальный рак (КРР) занимает одно из ведущих мест в структуре онкологической заболеваемости, в том числе в азиатских странах. В Республике Казахстан прирост заболеваемости раком ободочной кишки за последнее десятилетие составил 23 %, раком прямой кишки  – 17 %. Несмотря на действующие программы скрининга  колоректального рака, продолжается поиск новых, в том числе сывороточных, маркеров для ранней диагностики, а у  пациентов с выявленным КРР – панелей маркеров для прогноза течения заболевания. </p><p>Целью исследования является изучение диагностической ценности и динамики сывороточных биомаркеров у больных КРР разных стадий. </p></sec><sec><title>Материал и методы</title><p>Материал и методы. Биомаркеры изучены  иммунофлуоресцентным методом с использованием технологии xMap, который включал в себя одновременное иммунофлуоресцентное определение на магнитных сферах CA125, CA15–3, CA19–9, CEA, CYFRA21–1, sFAS, sFasL, HE4,  Остеопонтин, VEGF-A, pd-L1. </p></sec><sec><title>Результаты</title><p>Результаты. Показано, что уровень исследованных  маркеров не имел значимых различий у здоровых лиц и у больных с неонкологической патологией толстой кишки. При КРР выявлена статистически значимая зависимость уровня только 2 биомаркеров – CEA и ОПН – от стадии заболевания. У больных КРР IV стадии наблюдается значимое повышение CA125 по сравнению с новообразованиями I–III стадий. Такие маркеры, как CA19–9, HE-4, CA15–3, CYFRA 21–1, наряду с CEA, могут быть предложены для применения в комплексной  диагностической панели. Полученные результаты  позволяют сделать вывод о диагностических перспективах  маркера pd-L1 при колоректальном раке. </p></sec></abstract><trans-abstract xml:lang="en"><sec><title> Introduction</title><p> Introduction. Colorectal cancer is one of the most common cancers worldwide. In the Republic of Kazakhstan, over the past decade, the incidence rates of colon and rectal cancers have increased by 23 % and 17 %, respectively. Although colorectal cancer screening rates have increased over time, it is necessary to identify new serum markers for early detection and prognosis of this cancer. </p><p>The aim of the study was to evaluate the  diagnostic value of serum biomarkers for colorectal cancer. </p></sec><sec><title>Material and Methods</title><p>Material and Methods. Biomarkers were studied by immunofluorescence method using xMap technology, which included simultaneous immunofluorescence determination on magnetic spheres CA125, CA15–3, CA19–9, CEA, CYFRA21–1, sFAS, sFasL, HE4, Osteopontin, VEGF-A, pd-L1. </p></sec><sec><title>Results</title><p>Results. The study showed no significant differences in the levels of markersbetween healthy subjects (control group) and patients with bowel diseases. In cancer patients, СEA and OpN markers increased with increasing tumor stage, and were significantly higher than those observed in patients with bowel diseases and controls. The CA125 marker was significantly higher in patients with stage IV cancer then in patients with I–III stages. </p></sec><sec><title>Conclusion</title><p>Conclusion. Our study revealed that the new pd-L1 marker can serve as a significant biomarker for colorectal cancer. </p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>колоректальный рак</kwd><kwd>онкомаркеры</kwd><kwd>CEA</kwd><kwd>pD-L1</kwd><kwd>остеопонтин</kwd></kwd-group><kwd-group xml:lang="en"><kwd>colorectal cancer</kwd><kwd>oncomarker</kwd><kwd>biomarker</kwd><kwd>laboratory diagnostics</kwd><kwd>CEA</kwd><kwd>pD-L1</kwd><kwd>osteopontin</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа выполнена в рамках НТП О.0821 «Персонифицированный подход в управлении ряда значимых заболеваний», финансируемой МОН РК.</funding-statement><funding-statement xml:lang="en">The study was carried out within the framework of the program «Personalized approach to the management of diseases» funded by the Ministry of Education and Science of the Republic of Kazakhstan.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Brody H. Colorectal cancer. Nature. 2015 May 14; 521(7551): S1. doi: 10.1038/521S1a. PMID: 25970450.</mixed-citation><mixed-citation xml:lang="en">Brody H. Colorectal cancer. Nature. 2015 May 14; 521(7551): S1. doi: 10.1038/521S1a. PMID: 25970450.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin D.M., Forman D., Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1; 136(5): E359–86. doi: 10.1002/ijc.29210.</mixed-citation><mixed-citation xml:lang="en">Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin D.M., Forman D., Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1; 136(5): E359–86. doi: 10.1002/ijc.29210.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Одинцова И.Н., Черемисина О.В., Писарева Л.Ф., Спивакова И.О., Вусик М.В. Эпидемиология колоректального рака в Томской области. Сибирский онкологический журнал. 2017; 16(4): 89–95. doi: 10.21294/1814-4861-2017-16-4-89-95.</mixed-citation><mixed-citation xml:lang="en">Odintsova I.N., Cheremisina O.V., Pisareva L.F., Spivakova I.O., Vusik M.V. Epidemiology of colorectal cancer in Tomsk region. Siberian Journal of Oncology. 2017; 16(4): 89–95. (in Russian). doi: 10.21294/1814-4861-2017-16-4-89-95.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Показатели онкологической службы Республики Казахстан за 2017 год (статистические материалы). КазНИИОиР. 2018. 128 с.</mixed-citation><mixed-citation xml:lang="en">Indicators of the cancer service of the Republic of Kazakhstan for 2017 (statistical materials). KIOR. 2018. 128 р. (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Дохдырбай М., Есентаева С.Е., Толеуханов Т.С., Бисмильдина Г.С., Умбетьярова Л.Б. Анализ заболеваемости колоректальным раком в Республике Казахстан в 2009–2013 гг. Вестник КазНМУ. 2016; 1: 704–709.</mixed-citation><mixed-citation xml:lang="en">Dokhdyrbai M., Esentaeva S.E., Toleukhanov T.S., Bismildina G.S., Umbetyarova L.B. Analysis of the incidence of colorectal cancer in the Republic of Kazakhstan in 2009–2013. KazNMU Bulletin. 2016; 1: 704–709. (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Yotsukura S., Mamitsuka H. Evaluation of serum-based cancer biomarkers: a brief review from a clinical and computational viewpoint. Crit Rev Oncol Hematol. 2015 Feb; 93(2): 103–15. doi: 10.1016/j.critrevonc.2014.10.002.</mixed-citation><mixed-citation xml:lang="en">Yotsukura S., Mamitsuka H. Evaluation of serum-based cancer biomarkers: a brief review from a clinical and computational viewpoint. Crit Rev Oncol Hematol. 2015 Feb; 93(2): 103–15. doi: 10.1016/j.critrevonc.2014.10.002.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Lou E., Vogel R.I., Teoh D., Hoostal S., Grad A., Gerber M., Monu M., Lukaszewski T., Deshpande J., Linden M.A., Geller M.A. Assessment of Circulating Tumor Cells as a Predictive Biomarker of Histology in Women With Suspected Ovarian Cancer. Lab Med. 2018; 49(2): 134–9. doi: 10.1093/labmed/lmx084.</mixed-citation><mixed-citation xml:lang="en">Lou E., Vogel R.I., Teoh D., Hoostal S., Grad A., Gerber M., Monu M., Lukaszewski T., Deshpande J., Linden M.A., Geller M.A. Assessment of Circulating Tumor Cells as a Predictive Biomarker of Histology in Women With Suspected Ovarian Cancer. Lab Med. 2018; 49(2): 134–9. doi: 10.1093/labmed/lmx084.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Voith von Voithenberg L., Crocetti E., Martos C., Dimitrova N., Giusti F., Randi G., Rooney R., Dyba T., Bettio M., Negrão Carvalho R. Cancer registries guardians of breast cancer biomarker information: A systematic review. Int J Biol Markers. 2019 Jun; 34(2): 194–199. doi: 10.1177/1724600819836097.</mixed-citation><mixed-citation xml:lang="en">Voith von Voithenberg L., Crocetti E., Martos C., Dimitrova N., Giusti F., Randi G., Rooney R., Dyba T., Bettio M., Negrão Carvalho R. Cancer registries guardians of breast cancer biomarker information: A systematic review. Int J Biol Markers. 2019 Jun; 34(2): 194–199. doi: 10.1177/1724600819836097.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Otoshi T., Nagano T., Tachihara M., Nishimura Y. Possible Biomarkers for Cancer Immunotherapy. Cancers (Basel). 2019; 11(7): 935. doi: 10.3390/cancers1107093.</mixed-citation><mixed-citation xml:lang="en">Otoshi T., Nagano T., Tachihara M., Nishimura Y. Possible Biomarkers for Cancer Immunotherapy. Cancers (Basel). 2019; 11(7): 935. doi: 10.3390/cancers1107093.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">George A.P., Kuzel T.M., Zhang Y., Zhang B. The Discovery of Biomarkers in Cancer Immunotherapy. Comput Struct Biotechnol J. 2019 Apr 4; 17: 484–97. doi: 10.1016/j.csbj.2019.03.015.</mixed-citation><mixed-citation xml:lang="en">George A.P., Kuzel T.M., Zhang Y., Zhang B. The Discovery of Biomarkers in Cancer Immunotherapy. Comput Struct Biotechnol J. 2019 Apr 4; 17: 484–97. doi: 10.1016/j.csbj.2019.03.015.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Pellino G., Gallo G., Pallante P., Capasso R., De Stefano A., Maretto I., Malapelle U., Qiu S., Nikolaou S., Barina A., Clerico G., Reginelli A., Giuliani A., Sciaudone G., Kontovounisios C., Brunese L., Trompetto M., Selvaggi F. Noninvasive Biomarkers of Colorectal Cancer: Role in Diagnosis and Personalised Treatment Perspectives. Gastroenterol Res Pract. 2018 Jun 13; 2018: 2397863. doi: 10.1155/2018/2397863.</mixed-citation><mixed-citation xml:lang="en">Pellino G., Gallo G., Pallante P., Capasso R., De Stefano A., Maretto I., Malapelle U., Qiu S., Nikolaou S., Barina A., Clerico G., Reginelli A., Giuliani A., Sciaudone G., Kontovounisios C., Brunese L., Trompetto M., Selvaggi F. Noninvasive Biomarkers of Colorectal Cancer: Role in Diagnosis and Personalised Treatment Perspectives. Gastroenterol Res Pract. 2018 Jun 13; 2018: 2397863. doi: 10.1155/2018/2397863.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Nikolaou S., Qiu S., Fiorentino F., Rasheed S., Tekkis P., Kontovounisios C. Systematic review of blood diagnostic markers in colorectal cancer. Tech Coloproctol. 2018 Jul; 22(7): 481–498. doi: 10.1007/s10151-018-1820-3.</mixed-citation><mixed-citation xml:lang="en">Nikolaou S., Qiu S., Fiorentino F., Rasheed S., Tekkis P., Kontovounisios C. Systematic review of blood diagnostic markers in colorectal cancer. Tech Coloproctol. 2018 Jul; 22(7): 481–498. doi: 10.1007/s10151-018-1820-3.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Tong G., Xu W., Zhang G., Liu J., Zheng Z, Chen Y., Niu P., Xu X. The role of tissue and serum carcinoembryonic antigen in stages I to III of colorectal cancer – A retrospective cohort study. Cancer Med. 2018; 7(11): 5327–38. doi: 10.1002/cam4.1814.</mixed-citation><mixed-citation xml:lang="en">Tong G., Xu W., Zhang G., Liu J., Zheng Z, Chen Y., Niu P., Xu X. The role of tissue and serum carcinoembryonic antigen in stages I to III of colorectal cancer – A retrospective cohort study. Cancer Med. 2018; 7(11): 5327–38. doi: 10.1002/cam4.1814.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Huang R.H., Quan Y.J., Chen J.H., Wang T.F., Xu M., Ye M., Yuan H., Zhang C.J., Liu X.J., Min Z.J. Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway. Cell Physiol Biochem. 2017; 41(5): 1851–1864. doi: 10.1159/000471933.</mixed-citation><mixed-citation xml:lang="en">Huang R.H., Quan Y.J., Chen J.H., Wang T.F., Xu M., Ye M., Yuan H., Zhang C.J., Liu X.J., Min Z.J. Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway. Cell Physiol Biochem. 2017; 41(5): 1851–1864. doi: 10.1159/000471933.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Kamal A., Darwish R.K., Saad S., Salama M., El-Baradie T.S, Mahmoud H.G., Elshiwy Y. Association of Osteopontin Gene Polymorphisms with Colorectal Cancer. Cancer Invest. 2017; 35(2): 71–7. doi: 10.1080/07357907.2016.1247454.</mixed-citation><mixed-citation xml:lang="en">Kamal A., Darwish R.K., Saad S., Salama M., El-Baradie T.S, Mahmoud H.G., Elshiwy Y. Association of Osteopontin Gene Polymorphisms with Colorectal Cancer. Cancer Invest. 2017; 35(2): 71–7. doi: 10.1080/07357907.2016.1247454.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Wei R., Wong J.P.C., Kwok H.F. Osteopontin a promising biomarker for cancer therapy. J Cancer. 2017 Jul 15; 8(12): 2173–2183. doi: 10.7150/jca.20480.</mixed-citation><mixed-citation xml:lang="en">Wei R., Wong J.P.C., Kwok H.F. Osteopontin a promising biomarker for cancer therapy. J Cancer. 2017 Jul 15; 8(12): 2173–2183. doi: 10.7150/jca.20480.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Peltonen R., Österlund P., Lempinen M., Nordin A., Stenman U.H., Isoniemi H. Postoperative CEA is a better prognostic marker than CA19-9, hCGβ or TATI after resection of colorectal liver metastases. Tumour Biol. 2018 Jan; 40(1): 1010428317752944. doi: 10.1177/1010428317752944.</mixed-citation><mixed-citation xml:lang="en">Peltonen R., Österlund P., Lempinen M., Nordin A., Stenman U.H., Isoniemi H. Postoperative CEA is a better prognostic marker than CA19-9, hCGβ or TATI after resection of colorectal liver metastases. Tumour Biol. 2018 Jan; 40(1): 1010428317752944. doi: 10.1177/1010428317752944.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Yu Z., Chen Z., Wu J., Li Z., Wu Y. Prognostic value of pretreatment serum carbohydrate antigen 19-9 level in patients with colorectal cancer: A meta-analysis. PLoS One. 2017; 12(11): e0188139. doi: 10.1371/journal.pone.0188139.</mixed-citation><mixed-citation xml:lang="en">Yu Z., Chen Z., Wu J., Li Z., Wu Y. Prognostic value of pretreatment serum carbohydrate antigen 19-9 level in patients with colorectal cancer: A meta-analysis. PLoS One. 2017; 12(11): e0188139. doi: 10.1371/journal.pone.0188139.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Kim N.H., Lee M.Y., Park J.H., Park D.I., Sohn C.I., Choi K., Jung Y.S. Serum CEA and CA 19-9 Levels are Associated with the Presence and Severity of Colorectal Neoplasia. Yonsei Med J. 2017 Sep; 58(5): 918–24. doi: 10.3349/ymj.2017.58.5.918.</mixed-citation><mixed-citation xml:lang="en">Kim N.H., Lee M.Y., Park J.H., Park D.I., Sohn C.I., Choi K., Jung Y.S. Serum CEA and CA 19-9 Levels are Associated with the Presence and Severity of Colorectal Neoplasia. Yonsei Med J. 2017 Sep; 58(5): 918–24. doi: 10.3349/ymj.2017.58.5.918.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Liang S., Chang L. Serum matrix metalloproteinase-9 level as a biomarker for colorectal cancer: a diagnostic meta-analysis. Biomark Med. 2018 Apr; 12(4): 393–402. doi: 10.2217/bmm-2017-0206.</mixed-citation><mixed-citation xml:lang="en">Liang S., Chang L. Serum matrix metalloproteinase-9 level as a biomarker for colorectal cancer: a diagnostic meta-analysis. Biomark Med. 2018 Apr; 12(4): 393–402. doi: 10.2217/bmm-2017-0206.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Thomas D.S., Fourkala E.O., Apostolidou S., Gunu R., Ryan A., Jacobs I., Menon U., Alderton W., Gentry-Maharaj A., Timms J.F. Evaluation of serum CEA, CYFRA21-1 and CA125 for the early detection of colorectal cancer using longitudinal preclinical samples. Br J Cancer. 2015 Jul 14; 113(2): 268–74. doi: 10.1038/bjc.2015.202.</mixed-citation><mixed-citation xml:lang="en">Thomas D.S., Fourkala E.O., Apostolidou S., Gunu R., Ryan A., Jacobs I., Menon U., Alderton W., Gentry-Maharaj A., Timms J.F. Evaluation of serum CEA, CYFRA21-1 and CA125 for the early detection of colorectal cancer using longitudinal preclinical samples. Br J Cancer. 2015 Jul 14; 113(2): 268–74. doi: 10.1038/bjc.2015.202.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Gao Y., Wang J., Zhou Y., Sheng S., Qian S.Y., Huo X. Evaluation of Serum CEA, CA19-9, CA72-4, CA125 and Ferritin as Diagnostic Markers and Factors of Clinical Parameters for Colorectal Cancer. Sci Rep. 2018 Feb 9; 8(1): 2732. doi: 10.1038/s41598-018-21048-y.</mixed-citation><mixed-citation xml:lang="en">Gao Y., Wang J., Zhou Y., Sheng S., Qian S.Y., Huo X. Evaluation of Serum CEA, CA19-9, CA72-4, CA125 and Ferritin as Diagnostic Markers and Factors of Clinical Parameters for Colorectal Cancer. Sci Rep. 2018 Feb 9; 8(1): 2732. doi: 10.1038/s41598-018-21048-y.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Chang S.J., Ge X.S., Xu Z.Y., Qi X.W., Chen X.P. Lower serum CA125 level, negative vascular invasion, and wild BRAF were strongly associated with better 2-year disease-free survival in patients with stage III colorectal cancer who received adjuvant chemotherapy. Cancer Biomark. 2018; 22(1): 161–8. doi: 10.3233/CBM-181179.</mixed-citation><mixed-citation xml:lang="en">Chang S.J., Ge X.S., Xu Z.Y., Qi X.W., Chen X.P. Lower serum CA125 level, negative vascular invasion, and wild BRAF were strongly associated with better 2-year disease-free survival in patients with stage III colorectal cancer who received adjuvant chemotherapy. Cancer Biomark. 2018; 22(1): 161–8. doi: 10.3233/CBM-181179.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Huang C.J., Jiang J.K., Chang S.C., Lin J.K., Yang S.H. Serum CA125 concentration as a predictor of peritoneal dissemination of colorectal cancer in men and women. Medicine (Baltimore). 2016 Nov; 95(47): e5177. doi: 10.1097/MD.0000000000005177.</mixed-citation><mixed-citation xml:lang="en">Huang C.J., Jiang J.K., Chang S.C., Lin J.K., Yang S.H. Serum CA125 concentration as a predictor of peritoneal dissemination of colorectal cancer in men and women. Medicine (Baltimore). 2016 Nov; 95(47): e5177. doi: 10.1097/MD.0000000000005177.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Kemal Y.N., Demirag G.N., Bedir A.M., Tomak L., Derebey M., Erdem D.L., Gör U., Yücel I. Serum human epididymis protein 4 levels in colorectal cancer patients. Mol Clin Oncol. 2017 Sep; 7(3): 481–485. doi: 10.3892/mco.2017.1332.</mixed-citation><mixed-citation xml:lang="en">Kemal Y.N., Demirag G.N., Bedir A.M., Tomak L., Derebey M., Erdem D.L., Gör U., Yücel I. Serum human epididymis protein 4 levels in colorectal cancer patients. Mol Clin Oncol. 2017 Sep; 7(3): 481–485. doi: 10.3892/mco.2017.1332.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Cao H., Fang X., Li H., Li H., Kong J. Ultrasensitive detection of mucin 1 biomarker by immuno-loop-mediated isothermal amplification. Talanta. 2017 Mar 1; 164: 588–592. doi: 10.1016/j.talanta.2016.07.018.</mixed-citation><mixed-citation xml:lang="en">Cao H., Fang X., Li H., Li H., Kong J. Ultrasensitive detection of mucin 1 biomarker by immuno-loop-mediated isothermal amplification. Talanta. 2017 Mar 1; 164: 588–592. doi: 10.1016/j.talanta.2016.07.018.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Attallah A.M., El-Far M., Ibrahim A.R., El-Desouky M.A., Omran M.M., Elbendary M.S., Attallah K.A., Qura E.R., Abdallah S.O. Clinical value of a diagnostic score for colon cancer based on serum CEA, CA19-9, cytokeratin-1 and mucin-1. Br J Biomed Sci. 2018; 75(3): 122–7. doi: 10.1080/09674845.2018.1456309.</mixed-citation><mixed-citation xml:lang="en">Attallah A.M., El-Far M., Ibrahim A.R., El-Desouky M.A., Omran M.M., Elbendary M.S., Attallah K.A., Qura E.R., Abdallah S.O. Clinical value of a diagnostic score for colon cancer based on serum CEA, CA19-9, cytokeratin-1 and mucin-1. Br J Biomed Sci. 2018; 75(3): 122–7. doi: 10.1080/09674845.2018.1456309.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Goulart A., Ferreira C., Rodrigues A., Coimbra B., Sousa N., Leão P. The correlation between serum vascular endothelial growth factor (VEGF) and tumor VEGF receptor 3 in colorectal cancer. Ann Surg Treat Res. 2019 Jul; 97(1): 15–20. doi: 10.4174/astr.2019.97.1.15.</mixed-citation><mixed-citation xml:lang="en">Goulart A., Ferreira C., Rodrigues A., Coimbra B., Sousa N., Leão P. The correlation between serum vascular endothelial growth factor (VEGF) and tumor VEGF receptor 3 in colorectal cancer. Ann Surg Treat Res. 2019 Jul; 97(1): 15–20. doi: 10.4174/astr.2019.97.1.15.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Xu H., Ren Y.J., Liu K., Min X.L., Yang L., Zhou Y., Zheng J., Yang C. Correlations of serum VEGF and MMP-2 levels with CLM in CRC patients and effects of TACE on their expressions. Eur Rev Med Pharmacol Sci. 2018 Jun; 22(11): 3394–3401. doi: 10.26355/eurrev_201806_15161.</mixed-citation><mixed-citation xml:lang="en">Xu H., Ren Y.J., Liu K., Min X.L., Yang L., Zhou Y., Zheng J., Yang C. Correlations of serum VEGF and MMP-2 levels with CLM in CRC patients and effects of TACE on their expressions. Eur Rev Med Pharmacol Sci. 2018 Jun; 22(11): 3394–3401. doi: 10.26355/eurrev_201806_15161.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Karpuz T., Araz M., Korkmaz L., Kılınc I., Findik S., Karaagaç M., Eryilmaz M.K., Artac M. The Prognostic Value of Serum Semaphorin3A and VEGF Levels in Patients with Metastatic Colorectal Cancer. J Gastrointest Cancer. 2020 Jun; 51(2): 491–497. doi: 10.1007/s12029-019-00263-4.</mixed-citation><mixed-citation xml:lang="en">Karpuz T., Araz M., Korkmaz L., Kılınc I., Findik S., Karaagaç M., Eryilmaz M.K., Artac M. The Prognostic Value of Serum Semaphorin3A and VEGF Levels in Patients with Metastatic Colorectal Cancer. J Gastrointest Cancer. 2020 Jun; 51(2): 491–497. doi: 10.1007/s12029-019-00263-4.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Chen H., Qian J., Werner S., Cuk K., Knebel P., Brenner H. Development and validation of a panel of five proteins as blood biomarkers for early detection of colorectal cancer. Clin Epidemiol. 2017; 9: 517–26. doi: 10.2147/CLEP.S144171.</mixed-citation><mixed-citation xml:lang="en">Chen H., Qian J., Werner S., Cuk K., Knebel P., Brenner H. Development and validation of a panel of five proteins as blood biomarkers for early detection of colorectal cancer. Clin Epidemiol. 2017; 9: 517–26. doi: 10.2147/CLEP.S144171.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Sun C., Mezzadra R., Schumacher T.N. Regulation and Function of the PD-L1 Checkpoint. Immunity. 2018; 48(3): 434–52. doi: 10.1016/j.immuni.2018.03.014.</mixed-citation><mixed-citation xml:lang="en">Sun C., Mezzadra R., Schumacher T.N. Regulation and Function of the PD-L1 Checkpoint. Immunity. 2018; 48(3): 434–52. doi: 10.1016/j.immuni.2018.03.014.</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>
