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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

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Volume 54, Issue 8 (Aug 2016)


SOX17 promoter methylation in plasma circulating tumor DNA of patients with non-small cell lung cancer

Ioanna Balgkouranidou
  • Analysis of Circulating Tumor Cells Lab, Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Athens, Greece
  • Department of Medical Oncology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
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/ Maria Chimonidou
  • Analysis of Circulating Tumor Cells Lab, Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Athens, Greece
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/ Georgia Milaki
  • Department of Medical Oncology, University Hospital of Heraklion, Medical School, University of Crete, Heraklion, Greece
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/ Emily Tsaroucha
  • 8th Department of Pulmonary Diseases, “Sotiria” General Hospital for Chest Diseases, Athens, Greece
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/ Stylianos Kakolyris
  • Department of Medical Oncology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
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/ Vasilis Georgoulias
  • Department of Medical Oncology, University Hospital of Heraklion, Medical School, University of Crete, Heraklion, Greece
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/ Evi Lianidou
  • Corresponding author
  • Analysis of Circulating Tumor Cells Lab, Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Athens, Greece
  • Email
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Published Online: 2016-01-07 | DOI: https://doi.org/10.1515/cclm-2015-0776


Background: SOX17 belongs to the high-mobility group-box transcription factor superfamily and down-regulates the Wnt pathway. The aim of our study was to evaluate the prognostic significance of SOX17 promoter methylation in circulating tumor DNA (ctDNA) in plasma of non-small cell lung cancer (NSCLC) patients.

Methods: We examined the methylation status of SOX17 promoter in 57 operable NSCLC primary tumors and paired adjacent non-cancerous tissues and in ctDNA isolated from 48 corresponding plasma samples as well as in plasma from 74 patients with advanced NSCLC and 49 healthy individuals. SOX17 promoter methylation was examined by Methylation Specific PCR (MSP).

Results: In operable NSCLC, SOX17 promoter was fully methylated in primary tumors (57/57, 100%), and in corresponding ctDNA (27/48, 56.2%) while it was detected in only 1/49 (2.0%) healthy individuals. In advanced NSCLC, SOX17 promoter was methylated in ctDNA in 27/74 (36.4%) patients and OS was significantly different in favor of patients with non-methylated SOX17 promoter (p=0.012). Multivariate analysis revealed that SOX17 promoter methylation in ctDNA was an independent prognostic factor associated with OS in patients with advanced but not operable NSCLC.

Conclusions: Our results show that SOX17 promoter is highly methylated in primary tumors and in corresponding plasma samples both in operable and advanced NSCLC. In the advanced setting, SOX17 promoter methylation in plasma ctDNA has a statistical significant influence on NSCLC patient’s survival time. Detection of SOX17 promoter methylation in plasma provides prognostic information and merits to be further evaluated as a circulating tumor biomarker in patients with operable and advanced NSCLC.

Keywords: cell free DNA; circulating tumor DNA; DNA methylation; methylation specific PCR; non-small cell lung cancer; prognostic significance; SOX17


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About the article

Corresponding author: Prof. Evi Lianidou, Analysis of Circulating Tumor Cells Lab, Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Athens, 15771, Greece, Phone: +30 210 7274319, Fax: +30 210 7274750, E-mail:

Received: 2015-08-10

Accepted: 2015-11-01

Published Online: 2016-01-07

Published in Print: 2016-08-01

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2015-0776.

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