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Circulating Cell-Free DNA as a Prognostic and Molecular Marker for Patients with Brain Tumors under Perillyl Alcohol-Based Therapy

Tumor infiltration into brain tissue usually remains undetected even by high-resolution imaging. Molecular markers are used to increase diagnostic accuracy, but with limited continuous monitoring application. We evaluated the potential of circulating cell-free DNA (cfDNA) as a molecular indicator of...

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Autores principales: Faria, Giselle, Silva, Emanuelle, Da Fonseca, Clovis, Quirico-Santos, Thereza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032335/
https://www.ncbi.nlm.nih.gov/pubmed/29848970
http://dx.doi.org/10.3390/ijms19061610
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author Faria, Giselle
Silva, Emanuelle
Da Fonseca, Clovis
Quirico-Santos, Thereza
author_facet Faria, Giselle
Silva, Emanuelle
Da Fonseca, Clovis
Quirico-Santos, Thereza
author_sort Faria, Giselle
collection PubMed
description Tumor infiltration into brain tissue usually remains undetected even by high-resolution imaging. Molecular markers are used to increase diagnostic accuracy, but with limited continuous monitoring application. We evaluated the potential of circulating cell-free DNA (cfDNA) as a molecular indicator of the response to therapy by the intranasal administration (ITN) of perillyl alcohol (POH) in brain tumors. The cohort included 130 healthy subjects arranged as control-paired groups and patients at terminal stages with glioblastoma (GBM, n = 122) or brain metastasis (BM, n = 55) from stage IV adenocarcinomas. Serum cfDNA was isolated and quantified by fluorimetry. Compared with the controls (40 ng/mL), patients with brain tumors before ITN-POH treatment had increased (p < 0.0001) cfDNA median levels: GBM (286 ng/mL) and BM (588 ng/mL). ITN-POH treatment was significantly correlated (rho = −0.225; p = 0.024) with survival of >6 months at a concentration of 599 ± 221 ng/mL and of <6 months at 1626 ± 505 ng/mL, but a sharp and abrupt increase of cfDNA and tumor recurrence occurred after ITN-POH discontinuation. Patients under continuous ITN-POH treatment and checked with brain magnetic resonance imaging (MRI) compatible with complete response had cfDNA levels similar to the controls. cfDNA may be used as a noninvasive prognostic and molecular marker for POH-based therapy in brain tumors and as an accurate screening tool for the early detection of tumor progression.
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spelling pubmed-60323352018-07-13 Circulating Cell-Free DNA as a Prognostic and Molecular Marker for Patients with Brain Tumors under Perillyl Alcohol-Based Therapy Faria, Giselle Silva, Emanuelle Da Fonseca, Clovis Quirico-Santos, Thereza Int J Mol Sci Article Tumor infiltration into brain tissue usually remains undetected even by high-resolution imaging. Molecular markers are used to increase diagnostic accuracy, but with limited continuous monitoring application. We evaluated the potential of circulating cell-free DNA (cfDNA) as a molecular indicator of the response to therapy by the intranasal administration (ITN) of perillyl alcohol (POH) in brain tumors. The cohort included 130 healthy subjects arranged as control-paired groups and patients at terminal stages with glioblastoma (GBM, n = 122) or brain metastasis (BM, n = 55) from stage IV adenocarcinomas. Serum cfDNA was isolated and quantified by fluorimetry. Compared with the controls (40 ng/mL), patients with brain tumors before ITN-POH treatment had increased (p < 0.0001) cfDNA median levels: GBM (286 ng/mL) and BM (588 ng/mL). ITN-POH treatment was significantly correlated (rho = −0.225; p = 0.024) with survival of >6 months at a concentration of 599 ± 221 ng/mL and of <6 months at 1626 ± 505 ng/mL, but a sharp and abrupt increase of cfDNA and tumor recurrence occurred after ITN-POH discontinuation. Patients under continuous ITN-POH treatment and checked with brain magnetic resonance imaging (MRI) compatible with complete response had cfDNA levels similar to the controls. cfDNA may be used as a noninvasive prognostic and molecular marker for POH-based therapy in brain tumors and as an accurate screening tool for the early detection of tumor progression. MDPI 2018-05-30 /pmc/articles/PMC6032335/ /pubmed/29848970 http://dx.doi.org/10.3390/ijms19061610 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Faria, Giselle
Silva, Emanuelle
Da Fonseca, Clovis
Quirico-Santos, Thereza
Circulating Cell-Free DNA as a Prognostic and Molecular Marker for Patients with Brain Tumors under Perillyl Alcohol-Based Therapy
title Circulating Cell-Free DNA as a Prognostic and Molecular Marker for Patients with Brain Tumors under Perillyl Alcohol-Based Therapy
title_full Circulating Cell-Free DNA as a Prognostic and Molecular Marker for Patients with Brain Tumors under Perillyl Alcohol-Based Therapy
title_fullStr Circulating Cell-Free DNA as a Prognostic and Molecular Marker for Patients with Brain Tumors under Perillyl Alcohol-Based Therapy
title_full_unstemmed Circulating Cell-Free DNA as a Prognostic and Molecular Marker for Patients with Brain Tumors under Perillyl Alcohol-Based Therapy
title_short Circulating Cell-Free DNA as a Prognostic and Molecular Marker for Patients with Brain Tumors under Perillyl Alcohol-Based Therapy
title_sort circulating cell-free dna as a prognostic and molecular marker for patients with brain tumors under perillyl alcohol-based therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032335/
https://www.ncbi.nlm.nih.gov/pubmed/29848970
http://dx.doi.org/10.3390/ijms19061610
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