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Folic-acid metabolism and DNA-repair phenotypes differ between neuroendocrine lung tumors and associate with aggressive subtypes, therapy resistance and outcome

PURPOSE: 25% of all lung cancer cases are neuroendocrine (NELC) including typical (TC) and atypical carcinoid (AC), large-cell neuroendocrine (LCNEC) and small cell lung cancer (SCLC). Prognostic and predictive biomarkers are lacking. EXPERIMENTAL DESIGN: Sixty patients were used for nCounter mRNA e...

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Autores principales: Henry Walter, Robert Fred, Mairinger, Fabian Dominik, Werner, Robert, Vollbrecht, Claudia, Hager, Thomas, Schmid, Kurt Werner, Wohlschlaeger, Jeremias, Christoph, Daniel Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991445/
https://www.ncbi.nlm.nih.gov/pubmed/27064343
http://dx.doi.org/10.18632/oncotarget.7737
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author Henry Walter, Robert Fred
Mairinger, Fabian Dominik
Werner, Robert
Vollbrecht, Claudia
Hager, Thomas
Schmid, Kurt Werner
Wohlschlaeger, Jeremias
Christoph, Daniel Christian
author_facet Henry Walter, Robert Fred
Mairinger, Fabian Dominik
Werner, Robert
Vollbrecht, Claudia
Hager, Thomas
Schmid, Kurt Werner
Wohlschlaeger, Jeremias
Christoph, Daniel Christian
author_sort Henry Walter, Robert Fred
collection PubMed
description PURPOSE: 25% of all lung cancer cases are neuroendocrine (NELC) including typical (TC) and atypical carcinoid (AC), large-cell neuroendocrine (LCNEC) and small cell lung cancer (SCLC). Prognostic and predictive biomarkers are lacking. EXPERIMENTAL DESIGN: Sixty patients were used for nCounter mRNA expression analysis of the folic-acid metabolism (ATIC, DHFR, FOLR1, FPGS, GART, GGT1, SLC19A1, TYMS) and DNA-repair (ERCC1, MLH1, MSH2, MSH6, XRCC1). Phenotypic classification classified tumors (either below or above the median expression level) with respect to the folic acid metabolism or DNA repair. RESULTS: Expression of FOLR1, FPGS, MLH1 and TYMS (each p<0.0001) differed significantly between all four tumor types. FOLR1 and FPGS associated with tumor differentiation (both p<0.0001), spread to regional lymph nodes (FOLR1 p=0.0001 and FPGS p=0.0038), OS and PFS (FOLR1 p<0.0050 for both and FPGS p<0.0004 for OS). Phenotypic sorting revealed the Ft-phenotype to be the most prominent expression profile in carcinoids, whereas SCLC presented nearly univocal with the fT and LCNEC with fT or ft. These results were significant for tumor subtype (p<0.0001). CONCLUSIONS: The assessed biomarkers and phenotypes allow for risk stratification (OS, PFS), diagnostic classification and enhance the biological understanding of the different subtypes of neuroendocrine tumors revealing potential new therapy options and clarifying known resistance mechanisms.
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spelling pubmed-49914452016-09-01 Folic-acid metabolism and DNA-repair phenotypes differ between neuroendocrine lung tumors and associate with aggressive subtypes, therapy resistance and outcome Henry Walter, Robert Fred Mairinger, Fabian Dominik Werner, Robert Vollbrecht, Claudia Hager, Thomas Schmid, Kurt Werner Wohlschlaeger, Jeremias Christoph, Daniel Christian Oncotarget Research Paper PURPOSE: 25% of all lung cancer cases are neuroendocrine (NELC) including typical (TC) and atypical carcinoid (AC), large-cell neuroendocrine (LCNEC) and small cell lung cancer (SCLC). Prognostic and predictive biomarkers are lacking. EXPERIMENTAL DESIGN: Sixty patients were used for nCounter mRNA expression analysis of the folic-acid metabolism (ATIC, DHFR, FOLR1, FPGS, GART, GGT1, SLC19A1, TYMS) and DNA-repair (ERCC1, MLH1, MSH2, MSH6, XRCC1). Phenotypic classification classified tumors (either below or above the median expression level) with respect to the folic acid metabolism or DNA repair. RESULTS: Expression of FOLR1, FPGS, MLH1 and TYMS (each p<0.0001) differed significantly between all four tumor types. FOLR1 and FPGS associated with tumor differentiation (both p<0.0001), spread to regional lymph nodes (FOLR1 p=0.0001 and FPGS p=0.0038), OS and PFS (FOLR1 p<0.0050 for both and FPGS p<0.0004 for OS). Phenotypic sorting revealed the Ft-phenotype to be the most prominent expression profile in carcinoids, whereas SCLC presented nearly univocal with the fT and LCNEC with fT or ft. These results were significant for tumor subtype (p<0.0001). CONCLUSIONS: The assessed biomarkers and phenotypes allow for risk stratification (OS, PFS), diagnostic classification and enhance the biological understanding of the different subtypes of neuroendocrine tumors revealing potential new therapy options and clarifying known resistance mechanisms. Impact Journals LLC 2016-02-26 /pmc/articles/PMC4991445/ /pubmed/27064343 http://dx.doi.org/10.18632/oncotarget.7737 Text en Copyright: © 2016 Henry Walter et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Henry Walter, Robert Fred
Mairinger, Fabian Dominik
Werner, Robert
Vollbrecht, Claudia
Hager, Thomas
Schmid, Kurt Werner
Wohlschlaeger, Jeremias
Christoph, Daniel Christian
Folic-acid metabolism and DNA-repair phenotypes differ between neuroendocrine lung tumors and associate with aggressive subtypes, therapy resistance and outcome
title Folic-acid metabolism and DNA-repair phenotypes differ between neuroendocrine lung tumors and associate with aggressive subtypes, therapy resistance and outcome
title_full Folic-acid metabolism and DNA-repair phenotypes differ between neuroendocrine lung tumors and associate with aggressive subtypes, therapy resistance and outcome
title_fullStr Folic-acid metabolism and DNA-repair phenotypes differ between neuroendocrine lung tumors and associate with aggressive subtypes, therapy resistance and outcome
title_full_unstemmed Folic-acid metabolism and DNA-repair phenotypes differ between neuroendocrine lung tumors and associate with aggressive subtypes, therapy resistance and outcome
title_short Folic-acid metabolism and DNA-repair phenotypes differ between neuroendocrine lung tumors and associate with aggressive subtypes, therapy resistance and outcome
title_sort folic-acid metabolism and dna-repair phenotypes differ between neuroendocrine lung tumors and associate with aggressive subtypes, therapy resistance and outcome
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991445/
https://www.ncbi.nlm.nih.gov/pubmed/27064343
http://dx.doi.org/10.18632/oncotarget.7737
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