Aptamers Selected to Postoperative Lung Adenocarcinoma Detect Circulating Tumor Cells in Human Blood

Тип публикации: статья из журнала

Год издания: 2015

Идентификатор DOI: 10.1038/mt.2015.108

Ключевые слова: aptamer, clusterin, defensin, histone H2B, lipocortin 2, lipocortin 5, tumor marker, vimentin, Article, binding affinity, cancer diagnosis, circulating tumor cell, controlled study, false negative result, false positive result, human, human cell, lung adenocarcinoma, lung metastasis, major clinical study, postoperative period, sensitivity and specificity

Аннотация: Circulating tumor cells (CTCs) are rare cells and valuable clinical markers of prognosis of metastasis formation and prediction of patient survival. Most CTC analyses are based on the antibody-based detection of a few epithelial markers; therefore miss an important portion of mesenchymal cancer cells circulating in blood. In this work, we selected and identified DNA aptamers as specific affinity probes that bind to lung adenocarcinoma cells derived from postoperative tissues. The unique feature of our selection strategy is that aptamers are produced for lung cancer cell biomarkers in their native state and conformation without previous knowledge of the biomarkers. The aptamers did not bind to normal lung cells and lymphocytes, and had very low affinity to A549 lung adenocarcinoma culture. We applied these aptamers to detect CTCs, apoptotic bodies, and microemboli in clinical samples of peripheral blood of lung cancer and metastatic lung cancer patients. We identified aptamer-associated protein biomarkers for lung cancer such as vimentin, annexin A2, annexin A5, histone 2B, neutrophil defensin, and clusterin. Tumor-specific aptamers can be produced for individual patients and synthesized many times during anticancer therapy, thereby opening up the possibility of personalized diagnostics.

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Издание

Журнал: MOLECULAR THERAPY

Выпуск журнала: Vol. 23, Is. 9

Номера страниц: 1486-1496

ISSN журнала: 15250016

Место издания: NEW YORK

Издатель: NATURE PUBLISHING GROUP

Авторы

  • Zamay G.S. (Krasnoyarsk Research Center, Siberian Branch Russian Academy of Sciences)
  • Zamay A.S. (Krasnoyarsk Research Center, Siberian Branch Russian Academy of Sciences)
  • Krat A.V. (Krasnoyarsk Regional Clinical Cancer Center Named after A.I. Kryzhanovsky)
  • Modestov A.A. (Krasnoyarsk Regional Clinical Cancer Center Named after A.I. Kryzhanovsky)
  • Wehbe M. (Department of Chemistry and Biomolecular Sciences, University of Ottawa)
  • Gargaun A. (Department of Chemistry and Biomolecular Sciences, University of Ottawa)
  • Muharemagic D. (Department of Chemistry and Biomolecular Sciences, University of Ottawa)
  • Berezovski M.V. (Department of Chemistry and Biomolecular Sciences, University of Ottawa)
  • Kolovskaya O.S. (Krasnoyarsk Research Center, Siberian Branch Russian Academy of Sciences)
  • Zamay T.N. (Siberian Federal University)
  • Glazyrin Y.E. (Krasnoyarsk State Medical University Named after Prof V.F. Voino-Yasenetsky)
  • Zubkova O. (Krasnoyarsk State Medical University Named after Prof V.F. Voino-Yasenetsky)
  • Spivak E. (Siberian Federal University)
  • Komarova M. (Krasnoyarsk State Medical University Named after Prof V.F. Voino-Yasenetsky)
  • Grigorieva V. (Siberian Federal University)
  • Savchenko A. (Siberian Federal University)

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