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Molecular Comparison of Imatinib-Naïve and Resistant Gastrointestinal Stromal Tumors: Differentially Expressed microRNAs and mRNAs

Despite the success of imatinib in advanced gastrointestinal stromal tumor (GIST) patients, 50% of the patients experience resistance within two years of treatment underscoring the need to get better insight into the mechanisms conferring imatinib resistance. Here the microRNA and mRNA expression pr...

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Autores principales: Amirnasr, Azadeh, Gits, Caroline M.M., van Kuijk, Patricia F., Smid, Marcel, Vriends, Anne L.M., Rutkowski, Piotr, Sciot, Raf, Schöffski, Patrick, Debiec-Rychter, Maria, Sleijfer, Stefan, Wiemer, Erik A. C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627192/
https://www.ncbi.nlm.nih.gov/pubmed/31238586
http://dx.doi.org/10.3390/cancers11060882
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author Amirnasr, Azadeh
Gits, Caroline M.M.
van Kuijk, Patricia F.
Smid, Marcel
Vriends, Anne L.M.
Rutkowski, Piotr
Sciot, Raf
Schöffski, Patrick
Debiec-Rychter, Maria
Sleijfer, Stefan
Wiemer, Erik A. C.
author_facet Amirnasr, Azadeh
Gits, Caroline M.M.
van Kuijk, Patricia F.
Smid, Marcel
Vriends, Anne L.M.
Rutkowski, Piotr
Sciot, Raf
Schöffski, Patrick
Debiec-Rychter, Maria
Sleijfer, Stefan
Wiemer, Erik A. C.
author_sort Amirnasr, Azadeh
collection PubMed
description Despite the success of imatinib in advanced gastrointestinal stromal tumor (GIST) patients, 50% of the patients experience resistance within two years of treatment underscoring the need to get better insight into the mechanisms conferring imatinib resistance. Here the microRNA and mRNA expression profiles in primary (imatinib-naïve) and imatinib-resistant GIST were examined. Fifty-three GIST samples harboring primary KIT mutations (exon 9; n = 11/exon 11; n = 41/exon 17; n = 1) and comprising imatinib-naïve (IM-n) (n = 33) and imatinib-resistant (IM-r) (n = 20) tumors, were analyzed. The microRNA expression profiles were determined and from a subset (IM-n, n = 14; IM-r, n = 15) the mRNA expression profile was established. Ingenuity pathway analyses were used to unravel biochemical pathways and gene networks in IM-r GIST. Thirty-five differentially expressed miRNAs between IM-n and IM-r GIST samples were identified. Additionally, miRNAs distinguished IM-r samples with and without secondary KIT mutations. Furthermore 352 aberrantly expressed genes were found in IM-r samples. Pathway and network analyses revealed an association of differentially expressed genes with cell cycle progression and cellular proliferation, thereby implicating genes and pathways involved in imatinib resistance in GIST. Differentially expressed miRNAs and mRNAs between IM-n and IM-r GIST were identified. Bioinformatic analyses provided insight into the genes and biochemical pathways involved in imatinib-resistance and highlighted key genes that may be putative treatment targets.
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spelling pubmed-66271922019-07-19 Molecular Comparison of Imatinib-Naïve and Resistant Gastrointestinal Stromal Tumors: Differentially Expressed microRNAs and mRNAs Amirnasr, Azadeh Gits, Caroline M.M. van Kuijk, Patricia F. Smid, Marcel Vriends, Anne L.M. Rutkowski, Piotr Sciot, Raf Schöffski, Patrick Debiec-Rychter, Maria Sleijfer, Stefan Wiemer, Erik A. C. Cancers (Basel) Article Despite the success of imatinib in advanced gastrointestinal stromal tumor (GIST) patients, 50% of the patients experience resistance within two years of treatment underscoring the need to get better insight into the mechanisms conferring imatinib resistance. Here the microRNA and mRNA expression profiles in primary (imatinib-naïve) and imatinib-resistant GIST were examined. Fifty-three GIST samples harboring primary KIT mutations (exon 9; n = 11/exon 11; n = 41/exon 17; n = 1) and comprising imatinib-naïve (IM-n) (n = 33) and imatinib-resistant (IM-r) (n = 20) tumors, were analyzed. The microRNA expression profiles were determined and from a subset (IM-n, n = 14; IM-r, n = 15) the mRNA expression profile was established. Ingenuity pathway analyses were used to unravel biochemical pathways and gene networks in IM-r GIST. Thirty-five differentially expressed miRNAs between IM-n and IM-r GIST samples were identified. Additionally, miRNAs distinguished IM-r samples with and without secondary KIT mutations. Furthermore 352 aberrantly expressed genes were found in IM-r samples. Pathway and network analyses revealed an association of differentially expressed genes with cell cycle progression and cellular proliferation, thereby implicating genes and pathways involved in imatinib resistance in GIST. Differentially expressed miRNAs and mRNAs between IM-n and IM-r GIST were identified. Bioinformatic analyses provided insight into the genes and biochemical pathways involved in imatinib-resistance and highlighted key genes that may be putative treatment targets. MDPI 2019-06-24 /pmc/articles/PMC6627192/ /pubmed/31238586 http://dx.doi.org/10.3390/cancers11060882 Text en © 2019 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
Amirnasr, Azadeh
Gits, Caroline M.M.
van Kuijk, Patricia F.
Smid, Marcel
Vriends, Anne L.M.
Rutkowski, Piotr
Sciot, Raf
Schöffski, Patrick
Debiec-Rychter, Maria
Sleijfer, Stefan
Wiemer, Erik A. C.
Molecular Comparison of Imatinib-Naïve and Resistant Gastrointestinal Stromal Tumors: Differentially Expressed microRNAs and mRNAs
title Molecular Comparison of Imatinib-Naïve and Resistant Gastrointestinal Stromal Tumors: Differentially Expressed microRNAs and mRNAs
title_full Molecular Comparison of Imatinib-Naïve and Resistant Gastrointestinal Stromal Tumors: Differentially Expressed microRNAs and mRNAs
title_fullStr Molecular Comparison of Imatinib-Naïve and Resistant Gastrointestinal Stromal Tumors: Differentially Expressed microRNAs and mRNAs
title_full_unstemmed Molecular Comparison of Imatinib-Naïve and Resistant Gastrointestinal Stromal Tumors: Differentially Expressed microRNAs and mRNAs
title_short Molecular Comparison of Imatinib-Naïve and Resistant Gastrointestinal Stromal Tumors: Differentially Expressed microRNAs and mRNAs
title_sort molecular comparison of imatinib-naïve and resistant gastrointestinal stromal tumors: differentially expressed micrornas and mrnas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627192/
https://www.ncbi.nlm.nih.gov/pubmed/31238586
http://dx.doi.org/10.3390/cancers11060882
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