<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article 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" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="review-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Journal of Clinical Practice</journal-id><journal-title-group><journal-title xml:lang="en">Journal of Clinical Practice</journal-title><trans-title-group xml:lang="ru"><trans-title>Клиническая практика</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2220-3095</issn><issn publication-format="electronic">2618-8627</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">688161</article-id><article-id pub-id-type="doi">10.17816/clinpract688161</article-id><article-id pub-id-type="edn">HVADZZ</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Reviews</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Научные обзоры</subject></subj-group><subj-group subj-group-type="article-type"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Differential diagnostics of non-small-cell and small-cell lung cancer: modern approaches and promising technologies</article-title><trans-title-group xml:lang="ru"><trans-title>Дифференциальная диагностика немелкоклеточного и мелкоклеточного рака лёгкого: современные подходы и перспективные технологии</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2925-9350</contrib-id><contrib-id contrib-id-type="spin">9374-8489</contrib-id><name-alternatives><name xml:lang="en"><surname>Konoshenko</surname><given-names>Maria Yu.</given-names></name><name xml:lang="ru"><surname>Коношенко</surname><given-names>Мария Юрьевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>PhD</p></bio><bio xml:lang="ru"><p>канд. биол. наук</p></bio><email>lacyjewelrymk@gmail.com</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0004-3004-8969</contrib-id><contrib-id contrib-id-type="spin">3627-2494</contrib-id><name-alternatives><name xml:lang="en"><surname>Shutko</surname><given-names>Ekaterina V.</given-names></name><name xml:lang="ru"><surname>Шутко</surname><given-names>Екатерина Викторовна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>katshutko@gmail.com</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3433-7261</contrib-id><contrib-id contrib-id-type="spin">9752-3241</contrib-id><name-alternatives><name xml:lang="en"><surname>Bryzgunova</surname><given-names>Olga E.</given-names></name><name xml:lang="ru"><surname>Брызгунова</surname><given-names>Ольга Евгеньевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>PhD</p></bio><bio xml:lang="ru"><p>канд. биол. наук</p></bio><email>olga.bryzgunova@niboch.nsc.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0003-9068-5401</contrib-id><name-alternatives><name xml:lang="en"><surname>Ilyushchenko</surname><given-names>Antonina A.</given-names></name><name xml:lang="ru"><surname>Илющенко</surname><given-names>Антонина Александровна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>Kdlmedwans@gmail.com</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0003-6679-9185</contrib-id><name-alternatives><name xml:lang="en"><surname>Danilova</surname><given-names>Yaroslava M.</given-names></name><name xml:lang="ru"><surname>Данилова</surname><given-names>Ярослава Михайловна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>yaroslava.danilova.82@mail.ru</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8899-4294</contrib-id><contrib-id contrib-id-type="spin">7473-0530</contrib-id><name-alternatives><name xml:lang="en"><surname>Gorbunkov</surname><given-names>Stanislav D.</given-names></name><name xml:lang="ru"><surname>Горбунков</surname><given-names>Станислав Дмитриевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, Assistant Professor</p></bio><bio xml:lang="ru"><p>д-р мед. наук, доцент</p></bio><email>sdgorbunkov@mail.ru</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3385-2632</contrib-id><contrib-id contrib-id-type="spin">6269-7990</contrib-id><name-alternatives><name xml:lang="en"><surname>Zykov</surname><given-names>Kirill A.</given-names></name><name xml:lang="ru"><surname>Зыков</surname><given-names>Кирилл Алексеевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, corresponding member of the Russian Academy of Sciences, Professor of the Russian Academy of Sciences</p></bio><bio xml:lang="ru"><p>д-р мед. наук, чл.-корр. РАН, профессор РАН</p></bio><email>kirillaz@inbox.ru</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0866-0252</contrib-id><contrib-id contrib-id-type="spin">4114-3170</contrib-id><name-alternatives><name xml:lang="en"><surname>Laktionov</surname><given-names>Pavel P.</given-names></name><name xml:lang="ru"><surname>Лактионов</surname><given-names>Павел Петрович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>PhD</p></bio><bio xml:lang="ru"><p>канд. биол. наук</p></bio><email>lakt@1bio.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Institute of Chemical Biology and Fundamental Medicine</institution></aff><aff><institution xml:lang="ru">Институт химической биологии и фундаментальной медицины</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Pulmonology Scientific Research Institute under Federal Medical and Biological Agency of Russsian Federation</institution></aff><aff><institution xml:lang="ru">Научно-исследовательский институт пульмонологии Федерального медико-биологического агентства</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2025-10-03" publication-format="electronic"><day>03</day><month>10</month><year>2025</year></pub-date><pub-date date-type="pub" iso-8601-date="2025-10-26" publication-format="electronic"><day>26</day><month>10</month><year>2025</year></pub-date><volume>16</volume><issue>3</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>71</fpage><lpage>87</lpage><history><date date-type="received" iso-8601-date="2025-07-25"><day>25</day><month>07</month><year>2025</year></date><date date-type="accepted" iso-8601-date="2025-08-31"><day>31</day><month>08</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2025, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2025, Эко-Вектор</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc-nd/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://clinpractice.ru/clinpractice/article/view/688161">https://clinpractice.ru/clinpractice/article/view/688161</self-uri><abstract xml:lang="en"><p>Lung cancer represents a heterogeneous group of malignant neoplasms, among which two main forms can be distinguished — the non-small-cell and the small-cell lung cancer. These subtypes significantly differ by the histological, the molecular-genetic and the clinical characteristics, which defines the necessity of precise differential diagnostics for selecting the optimal treatment tactics. The review highlights the modern methods of diagnostics for the non-small-cell and the small-cell lung cancer, including the instrumental diagnostics, the histological and immunohistochemical examinations. Special attention was paid to the pros and cons of the promising non- and minimally invasive approaches, such as the analysis of circulating tumor cells, of the extracellular DNA, of the miRNA, of the marker proteins, of the volatile organic compounds and of the modern medical visualization (radiomics). Despite the significant progress in developing new diagnostic approaches, the problems remain that are related to the heterogeneity of tumors, the limited accessibility of the materials of small-cell lung cancer and the necessity of standardizing the new methods. The promising direction seems to the integration of multimodal approaches, combining the fluid biopsy, radiomics and the algorithms of machine learning, which can increase the precision of diagnostics and optimize the personalized treatment of the patients with various subtypes of lung cancer.</p></abstract><trans-abstract xml:lang="ru"><p>Рак лёгкого представляет собой гетерогенную группу злокачественных новообразований, среди которых выделяют две основные формы — немелкоклеточный и мелкоклеточный рак лёгкого. Эти подтипы существенно различаются по гистологическим, молекулярно-генетическим и клиническим характеристикам, что определяет необходимость точной дифференциальной диагностики для выбора оптимальной тактики лечения. В обзоре рассматриваются современные методы диагностики немелкоклеточного и мелкоклеточного рака лёгкого, включая инструментальную диагностику, гистологическое и иммуногистохимическое исследование. Особое внимание уделено плюсам и минусам перспективных не- и малоинвазивных подходов, таких как анализ циркулирующих опухолевых клеток, внеклеточной ДНК, микроРНК, белковых маркеров, летучих органических соединений, современной медицинской визуализации (радиомики). Несмотря на значительные успехи в разработке новых диагностических подходов, сохраняются проблемы, связанные с гетерогенностью опухолей, ограниченной доступностью материала мелкоклеточного рака лёгкого и необходимостью стандартизации новых методов. Перспективным направлением представляется интеграция мультимодальных подходов, сочетающих жидкостную биопсию, радиомику и алгоритмы машинного обучения, что может повысить точность диагностики и оптимизировать персонализированное лечение пациентов с различными подтипами рака лёгкого.</p></trans-abstract><kwd-group xml:lang="en"><kwd>non-small-cell lung cancer</kwd><kwd>small-cell lung cancer</kwd><kwd>differential diagnostics</kwd><kwd>fluid biopsy</kwd><kwd>radiomics</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>немелкоклеточный рак лёгкого</kwd><kwd>мелкоклеточный рак лёгкого</kwd><kwd>дифференциальная диагностика</kwd><kwd>жидкостная биопсия</kwd><kwd>радиомика</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution xml:lang="en">Federal Medical-Biological Agency of Russia</institution></institution-wrap><institution-wrap><institution xml:lang="ru">Федеральное медико-биологическое агентство России</institution></institution-wrap></funding-source><award-id>388-03-2024-136</award-id></award-group><award-group><funding-source><institution-wrap><institution xml:lang="en">Ministry of Science and Higher Education of the Russian Federation</institution></institution-wrap><institution-wrap><institution xml:lang="ru">Министерство науки и высшего образования Российской Федерации</institution></institution-wrap></funding-source><award-id>075-03-2025-069</award-id></award-group></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>International Agency for Research on Cancer [Internet]. WHO Classification of Tumours Editorial Board. 5th ed. Vol. 5. Thoracic tumours. Lyon; 2021. 565 p. ISBN: 13.978-92-832-4506-3</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Клинические рекомендации. Злокачественное новообразование бронхов и лёгкого. Кодирование по Международной статистической классификации болезней и проблем, связанных со здоровьем: C34. Ассоциация онкологов России, Российское общество клинической онкологии, 2022. [Clinical recommendations. Malignant neoplasm of the bronchi and lungs. Coding according to the International Statistical Classification of Diseases and Related Health Problems: C34. Association of Oncologists of Russia, Russian Society of Clinical Oncology; 2022. (In Russ.)]. Режим доступа: https://cr.minzdrav.gov.ru/preview-cr/30_4 Дата обращения: 15.07.2025.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–263. doi: 10.3322/caac.21834 EDN: FRJDQH</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Siegel RL, Miller KD, Fuchs HE, Jemal A. Erratum to “Cancer statistics, 2021”. CA Cancer J Clin. 2021;71(4):359. doi: 10.3322/caac.21669 EDN: CQUTZD</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Lu DN, Jiang Y, Zhang WC, et al. Lung cancer incidence in both sexes across global areas: data from 1978 to 2017 and predictions up to 2035. BMC Pulm Med. 2025;25(1):281. doi: 10.1186/s12890-025-03748-0</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>GBD 2019 Tobacco Collaborators. Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990-2019: a systematic analysis from the Global Burden of Disease Study 2019. Lancet. 2021;397(10292):2337–2360. doi: 10.1016/S0140-6736(21)01282-4</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Ha SY, Choi SJ, Cho JH, et al. Lung cancer in never-smoker Asian females is driven by oncogenic mutations, most often involving EGFR. Oncotarget. 2015;6(7):5465–5474. doi: 10.18632/oncotarget.2925</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Islami F, Goding Sauer A, Miller KD, et al. Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States. CA Cancer J Clin. 2018;68(1):31–54. doi: 10.3322/caac.21440 EDN: YDXVDN</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249. doi: 10.3322/caac.21660</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Злокачественные новообразования в России в 2022 году / под ред. А.Д. Каприна, В.В. Старинского, А.О. Шахзадовой, И.В. Лисичниковой. Москва, 2023. 275 с. [Kaprin AD, Starinsky VV, Shakhzadova AO, Lisichnikova IV, editors. Malignant neoplasms in Russia in 2022. Moscow; 2023. 275 p. (In Russ.)]</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Zhang Y, Vaccarella S, Morgan E, et al. Global variations in lung cancer incidence by histological subtype in 2020. Lancet Oncol. 2023;24(11):1206–1218. doi: 10.1016/S1470-2045(23)00444-8</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Nooreldeen R, Bach H. Current and future development in lung cancer diagnosis. Int J Mol Sci. 2021;22(16):8661. doi: 10.3390/ijms22168661</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>ESMO Рекомендации для пациентов. Немелкоклеточный рак лёгкого (НМРЛ). 2019. 65 с. [ESMO Recommendations for patients. Non-small cell lung cancer (NSCLC). 2019. 65 p. (In Russ.)]. Режим доступа: https://www.rosoncoweb.ru/patients/guidelines/NSCLC/ Дата обращения: 15.07.2025.</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Nanavaty P, Alvarez MS, Alberts WM. Lung cancer screening: advantages, controversies, and applications. Cancer Control. 2014;21(1):9–14. doi: 10.1177/107327481402100102</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48. doi: 10.3322/caac.21763 EDN: SUTYDV</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>George J, Lim JS, Jang SJ, et al. Comprehensive genomic profiles of small cell lung cancer. Nature. 2015;524(7563):47–53. doi: 10.1038/nature14664 EDN: UOSZYD</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Melosky B, Kambartel K, Häntschel M, et al. Worldwide prevalence of epidermal growth factor receptor mutations in non-small cell lung cancer: a meta-analysis. Mol Diagn Ther. 2022;26(1):7–18. doi: 10.1007/s40291-021-00563-1 EDN: IBRURO</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Bironzo P, Cani M, Jacobs F, et al. Real-world retrospective study of KRAS mutations in advanced non-small cell lung cancer. Cancer. 2023;129(11):1662–1671. doi: 10.1002/cncr.34731 EDN: OQEYMZ</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Lin HM, Wu Y, Yin Y, et al. Real-world ALK testing trends in patients with advanced non-small-cell lung cancer in the United States. Clin Lung Cancer. 2023;24(1):e39–e49. doi: 10.1016/j.cllc.2022.09.010 EDN: OKLRIF</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Yuan H, Zou Z, Hao X, et al. A real-world study: therapeutic outcomes of ROS1-positive advanced NSCLC. Thorac Cancer. 2025;16(9):e70086. doi: 10.1111/1759-7714.70086</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Papavassiliou KA, Sofianidi AA, Gogou VA, et al. P53 and Rb aberrations in small cell lung cancer. Int J Mol Sci. 2024;25(5):2479. doi: 10.3390/ijms25052479 EDN: LSBPUA</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Pelosof LC, Gerber DE. Paraneoplastic syndromes: an approach to diagnosis and treatment. Mayo Clin Proc. 2010;85(9):838–854. doi: 10.4065/mcp.2010.0099</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Hamilton G, Rath B, Stickler S. Significance of circulating tumor cells in lung cancer: a narrative review. Transl Lung Cancer Res. 2023;12(4):877–894. doi: 10.21037/tlcr-22-712 EDN: TNMTHA</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Брызгунова О.Е., Лактионов П.П. Формирование пула циркулирующих ДНК крови: источники, особенности строения и циркуляции // Биомедицинская химия. 2015. Т. 61, № 4. С. 409–426. [Bryzgunova OE, Laktionov PP. Generation of blood circulating dnas: sources, features of struction and circulation. Biomedical Chemistry. 2015;61(4):409–426]. doi: 10.18097/PBMC20156104409 EDN: UIJMTL</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Wang L, Dumenil C, Julié C, et al. Molecular characterization of circulating tumor cells in lung cancer: moving beyond enumeration. Oncotarget. 2017;8(65):109818–109835. doi: 10.18632/oncotarget.22651 EDN: YEBMGD</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Hou JM, Krebs MG, Lancashire L, et al. Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer. J Clin Oncol. 2012;30(6):525–532. doi: 10.1200/JCO.2010.33.3716</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Hou JM, Greystoke A, Lancashire L, et al. Evaluation of circulating tumor cells and serological cell death biomarkers in small cell lung cancer patients undergoing chemotherapy. Am J Pathol. 2009;175(2):808–816. doi: 10.2353/ajpath.2009.090078</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Devriese LA, Bosma AJ, van de Heuvel MM, et al. Circulating tumor cell detection in advanced non-small cell lung cancer patients by multi-marker QPCR analysis. Lung Cancer. 2012;75(2):242–247. doi: 10.1016/j.lungcan.2011.07.003</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Wu C, Hao H, Li L, et al. Preliminary investigation of the clinical significance of detecting circulating tumor cells enriched from lung cancer patients. J Thorac Oncol. 2009;4(1):30–36. doi: 10.1097/JTO.0b013e3181914125</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>O’Shannessy DJ, Davis DW, Anderes K, Somers EB. Isolation of circulating tumor cells from multiple epithelial cancers with ApoStream® for detecting (or monitoring) the expression of folate receptor alpha. Biomark Insights. 2016;11:7–18. doi: 10.4137/BMI.S35075</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Vona G, Sabile A, Louha M, et al. Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulating tumor cells. Am J Pathol. 2000;156(1):57–63. doi: 10.1016/S0002-9440(10)64706-2</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Brägelmann J, Böhm S, Guthrie MR, et al. Family matters: how MYC family oncogenes impact small cell lung cancer. Cell Cycle. 2017;16(16):1489–1498. doi: 10.1080/15384101.2017.1339849 EDN: YHVLWD</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Dammert MA, Brägelmann J, Olsen RR, et al. MYC paralog-dependent apoptotic priming orchestrates a spectrum of vulnerabilities in small cell lung cancer. Nat Commun. 2019;10(1):3485. doi: 10.1038/s41467-019-11371-x EDN: EMKAMU</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Peifer M, Fernández-Cuesta L, Sos ML, et al. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet. 2012;44(10):1104–1110. doi: 10.1038/ng.2396</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Rudin CM, Durinck S, Stawiski EW, et al. Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat Genet. 2012;44(10):1111–1116. doi: 10.1038/ng.2405</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Bass AJ, Watanabe H, Mermel CH, et al. SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nat Genet. 2009;41(11):1238–1242. doi: 10.1038/ng.465</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Ramos AH, Dutt A, Mermel C, et al. Amplification of chromosomal segment 4q12 in non-small cell lung cancer. Cancer Biol Ther. 2009;8(21):2042–2050. doi: 10.4161/cbt.8.21.9764</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Rekhtman N, Paik PK, Arcila ME, et al. Clarifying the spectrum of driver oncogene mutations in biomarker-verified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations. Clin Cancer Res. 2012;18(4):1167–1176. doi: 10.1158/1078-0432.CCR-11-2109 EDN: PLFQRF</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Jibiki T, Nishimura H, Sengoku S, Kodama K. Regulations, open data and healthcare innovation: a case of MSK-IMPACT and its implications for better cancer care. Cancers (Basel). 2021;13(14):3448. doi: 10.3390/cancers13143448 EDN: XJYAIR</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>De Alves RC, Meurer RT, Roehe AV. MYC amplification is associated with poor survival in small cell lung cancer: a chromogenic in situ hybridization study. J Cancer Res Clin Oncol. 2014;140(12):2021–2025. doi: 10.1007/s00432-014-1769-1 EDN: IVJKOC</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>Wali A. FHIT: doubts are clear now. Sci World J. 2010;10:1142–1151. doi: 10.1100/tsw.2010.110</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>Karachaliou N, Rosell R, Viteri S. The role of SOX2 in small cell lung cancer, lung adenocarcinoma and squamous cell carcinoma of the lung. Transl Lung Cancer Res. 2013;2(3):172-179. doi: 10.3978/j.issn.2218-6751.2013.01.01</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>Ruiz-Patiño A, Castro CD, Ricaurte LM, et al. EGFR amplification and sensitizing mutations correlate with survival in lung adenocarcinoma patients treated with erlotinib (MutP-CLICaP). Targ Oncol. 2018;13(5):621–629. doi: 10.1007/s11523-018-0594-x EDN: MPQGSJ</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>Yang M, Mandal E, Liu FX, et al. Non-small cell lung cancer with MET amplification: review of epidemiology, associated disease characteristics, testing procedures, burden, and treatments. Front Oncol. 2024;13:1241402. doi: 10.3389/fonc.2023.1241402 EDN: VJJBZH</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>Chen Y, Huang Y, Gao X, et al. CCND1 amplification contributes to immunosuppression and is associated with a poor prognosis to immune checkpoint inhibitors in solid tumors. Front Immunol. 2020;11:1620. doi: 10.3389/fimmu.2020.01620 EDN: FYKKBZ</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>Wang S, Lai JC, Li Y, et al. Loss of CDKN2A enhances the efficacy of immunotherapy in EGFR-mutant non-small cell lung cancer. Cancer Res. 2025;85(3):585–601. doi: 10.1158/0008-5472.CAN-24-1817 EDN: VORDYW</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>Rolfo C, Mack P, Scagliotti GV, et al. Liquid biopsy for advanced NSCLC: a consensus statement from the international association for the study of lung cancer. J Thorac Oncol. 2021;16(10):1647–1662. doi: 10.1016/j.jtho.2021.06.017 EDN: VCZCQW</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>Брызгунова О.Е., Лактионов П.П. Современные методы исследования метилирования внеклеточных ДНК // Молекулярная биология. 2017. Т. 51, № 2. С. 195–214. [Bryzgunova OE, Laktionov PP. Current methods of extracellular DNA methylation analysis. Molecular Biology. 2017;51(2):195–214]. doi: 10.7868/S0026898417010074 EDN: VXNTAJ</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>Nunes SP, Diniz F, Moreira-Barbosa C, et al. Subtyping lung cancer using DNA methylation in liquid biopsies. J Clin Med. 2019;8(9):1500. doi: 10.3390/jcm8091500</mixed-citation></ref><ref id="B50"><label>50.</label><mixed-citation>Toyooka S, Toyooka KO, Maruyama R, et al. DNA methylation profiles of lung tumors. Mol Cancer Ther. 2001;1(1):61–67.</mixed-citation></ref><ref id="B51"><label>51.</label><mixed-citation>Heeke S, Gay CM, Estecio MR, et al. Tumor- and circulating-free DNA methylation identifies clinically relevant small cell lung cancer subtypes. Cancer Cell. 2024;42(2):225–237.e5. doi: 10.1016/j.ccell.2024.01.001 EDN: DOXQPA</mixed-citation></ref><ref id="B52"><label>52.</label><mixed-citation>Poirier JT, Gardner EE, Connis N, et al. DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2. Oncogene. 2015;34(48):5869–5878. doi: 10.1038/onc.2015.38 EDN: VFAHJH</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>Walter K, Holcomb T, Januario T, et al. DNA methylation profiling defines clinically relevant biological subsets of non-small cell lung cancer. Clin Cancer Res. 2012;18(8):2360–2373. doi: 10.1158/1078-0432.CCR-11-2635-T EDN: YCPGLL</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>Gao X, Jia M, Zhang Y, et al. DNA methylation changes of whole blood cells in response to active smoking exposure in adults: a systematic review of DNA methylation studies. Clin Epigenetics. 2015;7(1):113. doi: 10.1186/s13148-015-0148-3 EDN: ZLFZQF</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>Locke WJ, Guanzon D, Ma C, et al. DNA methylation cancer biomarkers: translation to the clinic. Front Genet. 2019;10:1150. doi: 10.3389/fgene.2019.01150 EDN: NLPPCO</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>Cui S, Ye L, Wang H, et al. Use of superARMS EGFR mutation detection kit to detect EGFR in plasma cell-free DNA of patients with lung adenocarcinoma. Clin Lung Cancer. 2018;19(3):e313–e322. doi: 10.1016/j.cllc.2017.12.009</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>Claus J, de Smet D, Breyne J, et al. Patient-centric thresholding of Cobas® EGFR mutation Test v2 for surveillance of EGFR-mutated metastatic non-small cell lung cancer. Sci Rep. 2024;14(1):18191. doi: 10.1038/s41598-024-68350-6 EDN: HRXGJZ</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>Zhang Q, Zheng K, Gao Y, et al. Plasma exosomal miR-1290 and miR-29c-3p as diagnostic biomarkers for lung cancer. Heliyon. 2023;9(10):e21059. doi: 10.1016/j.heliyon.2023.e21059 EDN: PHAFOU</mixed-citation></ref><ref id="B59"><label>59.</label><mixed-citation>Poroyko V, Mirzapoiazova T, Nam A, et al. Exosomal miRNAs species in the blood of small cell and non-small cell lung cancer patients. Oncotarget. 2018;9(28):19793–19806. doi: 10.18632/oncotarget.24857</mixed-citation></ref><ref id="B60"><label>60.</label><mixed-citation>Valadi H, Ekström K, Bossios A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–659. doi: 10.1038/ncb1596</mixed-citation></ref><ref id="B61"><label>61.</label><mixed-citation>Kumar MA, Baba SK, Sadida HQ, et al. Extracellular vesicles as tools and targets in therapy for diseases. Signal Transduct Target Ther. 2024;9(1):27. doi: 10.1038/s41392-024-01735-1 EDN: EPOTHG</mixed-citation></ref><ref id="B62"><label>62.</label><mixed-citation>Lin J, Wang Y, Zou YQ, et al. Differential miRNA expression in pleural effusions derived from extracellular vesicles of patients with lung cancer, pulmonary tuberculosis, or pneumonia. Tumour Biol. 2016;37(12):15835–15845. doi: 10.1007/s13277-016-5410-6 EDN: WARYQA</mixed-citation></ref><ref id="B63"><label>63.</label><mixed-citation>Müller Bark J, Kulasinghe A, Amenábar JM, Punyadeera C. Exosomes in cancer. Adv Clin Chem. 2021;101:1–40. doi: 10.1016/bs.acc.2020.06.006 EDN: IBIWAZ</mixed-citation></ref><ref id="B64"><label>64.</label><mixed-citation>Casagrande GM, Silva MO, Reis RM, Leal LF. Liquid biopsy for lung cancer: up-to-date and perspectives for screening programs. Int J Mol Sci. 2023;24(3):2505. doi: 10.3390/ijms24032505 EDN: NARGMH</mixed-citation></ref><ref id="B65"><label>65.</label><mixed-citation>Коношенко М.Ю., Лактионов П.П., Ланцухай Ю.А., и др. Малоинвазивная диагностика рака легкого на основе анализа внеклеточной микроРНК крови // Успехи молекулярной онкологии. 2023. Т. 10, № 2. С. 78–89. [Konoshenko MYu, Laktionov PP, Lancuhaj YuA, et al. Cell-free plasma miRNAs analysis for low invasive lung cancer diagnostics. Advances Molecular Oncology. 2023;10(2):78–89]. doi: 10.17650/2313-805X-2023-10-2-78-89 EDN: FSUWHT</mixed-citation></ref><ref id="B66"><label>66.</label><mixed-citation>Davenport ML, Kulkarni A, Wang J, et al. miRNA-31 is a genomic biomarker of molecular heterogeneity in lung adenocarcinoma. Cancer Res. 2021;81(7):1788–1800. doi: 10.1158/0008-5472.CAN-20-2769</mixed-citation></ref><ref id="B67"><label>67.</label><mixed-citation>Du L, Schageman JJ, Subauste MC, et al. miR-93, miR-98, and miR-197 regulate expression of tumor suppressor gene FUS1. Mol Cancer Res. 2010;8(6):873–883. doi: 10.1186/1756-9966-29-75</mixed-citation></ref><ref id="B68"><label>68.</label><mixed-citation>Gilad S, Lithwick-Yanai G, Barshack I, et al. Multicenter validation of a microRNA-based assay for diagnosing indeterminate thyroid nodules. J Mol Diagn. 2012;14(5):517–524. doi: 10.1016/j.jmoldx.2012.03.004</mixed-citation></ref><ref id="B69"><label>69.</label><mixed-citation>Powrózek T, Krawczyk P, Kowalski DM, et al. Plasma circulating microRNA-944 and microRNA-3662 as potential histologic type-specific early lung cancer biomarkers. Transl Res. 2015;166(4):315–323. doi: 10.1016/j.trsl.2015.05.009</mixed-citation></ref><ref id="B70"><label>70.</label><mixed-citation>Abdipourbozorgbaghi M, Vancura A, Radpour R, Haefliger S. Circulating miRNA panels as a novel non-invasive diagnostic, prognostic, and potential predictive biomarkers in non-small cell lung cancer (NSCLC). Br J Cancer. 2024;131(8):1350–1362. doi: 10.1038/s41416-024-02831-3 EDN: DLZGNR</mixed-citation></ref><ref id="B71"><label>71.</label><mixed-citation>Molina R, Filella X, Augé JM. ProGRP: a new biomarker for small cell lung cancer. Clin Biochem. 2004;37(7):505–511. doi: 10.1016/j.clinbiochem.2004.05.007</mixed-citation></ref><ref id="B72"><label>72.</label><mixed-citation>Isgrò MA, Bottoni P, Scatena R. Neuron-specific enolase as a biomarker: biochemical and clinical aspects. Adv Exp Med Biol. 2015;867:125–143. doi: 10.1007/978-94-017-7215-0_9</mixed-citation></ref><ref id="B73"><label>73.</label><mixed-citation>Dhanurdhar Y, Jagaty SK, Subhankar S, Behera D. Diagnostic and prognostic significance of serum biomarkers: serum amyloid A and CYFRA 21-1 in lung cancer. Int J Appl Basic Med Res. 2023;13(2):89–94. doi: 10.4103/ijabmr.ijabmr_639_22</mixed-citation></ref><ref id="B74"><label>74.</label><mixed-citation>Grunnet M, Sorensen JB. Carcinoembryonic antigen (CEA) as tumor marker in lung cancer. Lung Cancer. 2012;76(2):138–143. doi: 10.1016/j.lungcan.2011.11.012</mixed-citation></ref><ref id="B75"><label>75.</label><mixed-citation>Molina R, Auge JM, Escudero JM, et al. Mucins CA 125, CA 19.9, CA 15.3 and TAG-72.3 as tumor markers in patients with lung cancer: comparison with CYFRA 21-1, CEA, SCC and NSE. Tumour Biol. 2008;29(6):371–380. doi: 10.1159/000181180</mixed-citation></ref><ref id="B76"><label>76.</label><mixed-citation>Bi H, Yin L, Fang W, et al. Association of CEA, NSE, CYFRA 21-1, SCC-Ag, and ProGRP with clinicopathological characteristics and chemotherapeutic outcomes of lung cancer. Lab Med. 2023;54(4):372–379. doi: 10.1093/labmed/lmac122 EDN: WNNQGG</mixed-citation></ref><ref id="B77"><label>77.</label><mixed-citation>Zamay GS, Kolovskaya OS, Zukov RA, et al. Current and prospective protein biomarkers of lung cancer. Cancers (Basel). 2017;9(11):155. doi: 10.3390/cancers9110155 EDN: XNRJBS</mixed-citation></ref><ref id="B78"><label>78.</label><mixed-citation>Sandfeld-Paulsen B, Jakobsen KR, Bæk R, et al. Exosomal proteins as diagnostic biomarkers in lung cancer. J Thorac Oncol. 2016;11(10):1701–1710. doi: 10.1016/j.jtho.2016.05.034</mixed-citation></ref><ref id="B79"><label>79.</label><mixed-citation>Kondo K, Harada Y, Nakano M, et al. Identification of distinct N-glycosylation patterns on extracellular vesicles from small-cell and non-small-cell lung cancer cells. J Biol Chem. 2022;298(6):101950. doi: 10.1016/j.jbc.2022.101950 EDN: PZEZXF</mixed-citation></ref><ref id="B80"><label>80.</label><mixed-citation>Papakonstantinou D, Roumeliotou A, Pantazaka E, et al. Integrative analysis of circulating tumor cells (CTCs) and exosomes from small-cell lung cancer (SCLC) patients: a comprehensive approach. Mol Oncol. 2025;19(7):2038–2055. doi: 10.1002/1878-0261.13765 EDN: SSRPXY</mixed-citation></ref><ref id="B81"><label>81.</label><mixed-citation>Bao M, Huang Y, Lang Z, et al. Proteomic analysis of plasma exosomes in patients with non-small cell lung cancer. Transl Lung Cancer Res. 2022;11(7):1434–1452. doi: 10.21037/tlcr-22-467 EDN: TXPXHO</mixed-citation></ref><ref id="B82"><label>82.</label><mixed-citation>Hu Q, Li K, Yang C, et al. The role of artificial intelligence based on PET/CT radiomics in NSCLC. Front Oncol. 2023;13:1133164. doi: 10.3389/fonc.2023.1133164</mixed-citation></ref><ref id="B83"><label>83.</label><mixed-citation>Manafi-Farid R, Askari E, Shiri I, et al. [18F]FDG-PET/CT radiomics and artificial intelligence in lung cancer. Semin Nucl Med. 2022;52(6):759–780. doi: 10.1053/j.semnuclmed.2022.04.004 EDN: PWBTEU</mixed-citation></ref><ref id="B84"><label>84.</label><mixed-citation>Safarian A, Mirshahvalad SA, Nasrollahi H, et al. Impact of [18F]FDG PET/CT radiomics and artificial intelligence in clinical decision making in lung cancer. Semin Nucl Med. 2025;55(2):156–166. doi: 10.1053/j.semnuclmed.2025.02.006 EDN: BILMAT</mixed-citation></ref><ref id="B85"><label>85.</label><mixed-citation>Yang L, Xu P, Li M, et al. PET/CT radiomic features: a potential biomarker for EGFR mutation status and survival outcome prediction in NSCLC patients treated with TKIs. Front Oncol. 2022;12:894323. doi: 10.3389/fonc.2022.894323 EDN: LKPLSQ</mixed-citation></ref><ref id="B86"><label>86.</label><mixed-citation>Guo Y, Song Q, Jiang M, et al. Histological subtypes classification of lung cancers on CT images using 3D deep learning and radiomics. Acad Radiol. 2021;28(9):e258–e266. doi: 10.1016/j.acra.2020.06.010 EDN: PVFKUC</mixed-citation></ref><ref id="B87"><label>87.</label><mixed-citation>Shah RP, Selby HM, Mukherjee P, et al. Machine learning radiomics model for early identification of small-cell lung cancer on computed tomography scans. JCO Clin Cancer Inform. 2021;5:746–757. doi: 10.1200/CCI.21.00021 EDN: RVAUEI</mixed-citation></ref><ref id="B88"><label>88.</label><mixed-citation>E L, Lu L, Li L, et al. Radiomics for classification of lung cancer histological subtypes based on nonenhanced computed tomography. Acad Radiol. 2019;26(9):1245–1252. doi: 10.1016/j.acra.2018.10.013</mixed-citation></ref><ref id="B89"><label>89.</label><mixed-citation>Yang L, Yang J, Zhou X, et al. Development of a radiomics nomogram based on the 2D and 3D CT features to predict the survival of non-small cell lung cancer patients. Eur Radiol. 2019;29(5):2196–2206. doi: 10.1007/s00330-018-5770-y EDN: XDWKUS</mixed-citation></ref><ref id="B90"><label>90.</label><mixed-citation>Saalberg Y, Wolff M. VOC breath biomarkers in lung cancer. Clin Chim Acta. 2016;459:5–9. doi: 10.1016/j.cca.2016.05.013</mixed-citation></ref><ref id="B91"><label>91.</label><mixed-citation>Lv W, Shi W, Zhang Z, et al. Identification of volatile biomarkers for lung cancer from different histological sources: a comprehensive study. Anal Biochem. 2024;690:115527. doi: 10.1016/j.ab.2024.115527 EDN: WQNEIT</mixed-citation></ref><ref id="B92"><label>92.</label><mixed-citation>Fan X, Zhong R, Liang H, et al. Exhaled VOC detection in lung cancer screening: a comprehensive meta-analysis. BMC Cancer. 2024;24(1):775. doi: 10.1186/s12885-024-12537-7 EDN: UHYNDS</mixed-citation></ref><ref id="B93"><label>93.</label><mixed-citation>Jia Z, Zhang H, Ong CN, et al. Detection of lung cancer: concomitant volatile organic compounds and metabolomic profiling of six cancer cell lines. ACS Omega. 2018;3(5):5131–5140. doi: 10.1021/acsomega.7b02035</mixed-citation></ref><ref id="B94"><label>94.</label><mixed-citation>Oguma T, Nagaoka T, Kurahashi M, et al. Clinical contributions of exhaled volatile organic compounds in the diagnosis of lung cancer. PLoS One. 2017;12(4):e0174802. doi: 10.1371/journal.pone.0174802</mixed-citation></ref><ref id="B95"><label>95.</label><mixed-citation>Fuchs P, Loeseken C, Schubert JK, Miekisch W. Breath gas aldehydes as biomarkers of lung cancer. Int J Cancer. 2010;126(11):2663–2670. doi: 10.1002/ijc.24970 EDN: NYUUWF</mixed-citation></ref><ref id="B96"><label>96.</label><mixed-citation>Steenhuis EG, Asmara OD, Kort S, et al. The electronic nose in lung cancer diagnostics: a systematic review and meta-analysis. ERJ Open Res. 2025;11(3):00723–2024. doi: 10.1183/23120541.00723-2024 EDN: QQRQLW</mixed-citation></ref><ref id="B97"><label>97.</label><mixed-citation>Kort S, Tiggeloven MM, Brusse-Keizer M, et al. Multi-centre prospective study on diagnosing subtypes of lung cancer by exhaled-breath analysis. Lung Cancer. 2018;125:223–229. doi: 10.1016/j.lungcan.2018.09.022</mixed-citation></ref><ref id="B98"><label>98.</label><mixed-citation>Monedeiro F, Monedeiro-Milanowski M, Ratiu IA, et al. Needle trap device-GC-MS for characterization of lung diseases based on breath VOC profiles. Molecules. 2021;26(6):1789. doi: 10.3390/molecules26061789 EDN: RVIHQL</mixed-citation></ref><ref id="B99"><label>99.</label><mixed-citation>Amann A, Costello BD, Miekisch W, et al. The human volatilome: volatile organic compounds (VOCs) in exhaled breath, skin emanations, urine, feces and saliva. J Breath Res. 2014;8(3):034001. doi: 10.1088/1752-7155/8/3/034001 EDN: YARLEG</mixed-citation></ref><ref id="B100"><label>100.</label><mixed-citation>Rondanelli M, Perdoni F, Infantino V, et al. Volatile organic compounds as biomarkers of gastrointestinal diseases and nutritional status. J Anal Methods Chem. 2019;2019:7247802. doi: 10.1155/2019/7247802</mixed-citation></ref></ref-list></back></article>
