Gene signature associated with benign neurofibroma transformation to malignant peripheral nerve sheath tumors.
Benign neurofibromas, the main phenotypic manifestations of the rare neurological disorder neurofibromatosis type 1, degenerate to malignant tumors associated to poor prognosis in about 10% of patients. Despite efforts in the field of (epi)genomics, the lack of prognostic biomarkers with which to pr...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5443557?pdf=render |
| _version_ | 1818485065778200576 |
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| author | Marta Martínez Carlos O S Sorzano Alberto Pascual-Montano Jose M Carazo |
| author_facet | Marta Martínez Carlos O S Sorzano Alberto Pascual-Montano Jose M Carazo |
| author_sort | Marta Martínez |
| collection | DOAJ |
| description | Benign neurofibromas, the main phenotypic manifestations of the rare neurological disorder neurofibromatosis type 1, degenerate to malignant tumors associated to poor prognosis in about 10% of patients. Despite efforts in the field of (epi)genomics, the lack of prognostic biomarkers with which to predict disease evolution frustrates the adoption of appropriate early therapeutic measures. To identify potential biomarkers of malignant neurofibroma transformation, we integrated four human experimental studies and one for mouse, using a gene score-based meta-analysis method, from which we obtained a score-ranked signature of 579 genes. Genes with the highest absolute scores were classified as promising disease biomarkers. By grouping genes with similar neurofibromatosis-related profiles, we derived panels of potential biomarkers. The addition of promoter methylation data to gene profiles indicated a panel of genes probably silenced by hypermethylation. To identify possible therapeutic treatments, we used the gene signature to query drug expression databases. Trichostatin A and other histone deacetylase inhibitors, as well as cantharidin and tamoxifen, were retrieved as putative therapeutic means to reverse the aberrant regulation that drives to malignant cell proliferation and metastasis. This in silico prediction corroborated reported experimental results that suggested the inclusion of these compounds in clinical trials. This experimental validation supported the suitability of the meta-analysis method used to integrate several sources of public genomic information, and the reliability of the gene signature associated to the malignant evolution of neurofibromas to generate working hypotheses for prognostic and drug-responsive biomarkers or therapeutic measures, thus showing the potential of this in silico approach for biomarker discovery. |
| first_indexed | 2024-12-10T16:03:06Z |
| format | Article |
| id | doaj.art-7680558eb7794a788351bcb75c0bf63a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T16:03:06Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7680558eb7794a788351bcb75c0bf63a2022-12-22T01:42:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01125e017831610.1371/journal.pone.0178316Gene signature associated with benign neurofibroma transformation to malignant peripheral nerve sheath tumors.Marta MartínezCarlos O S SorzanoAlberto Pascual-MontanoJose M CarazoBenign neurofibromas, the main phenotypic manifestations of the rare neurological disorder neurofibromatosis type 1, degenerate to malignant tumors associated to poor prognosis in about 10% of patients. Despite efforts in the field of (epi)genomics, the lack of prognostic biomarkers with which to predict disease evolution frustrates the adoption of appropriate early therapeutic measures. To identify potential biomarkers of malignant neurofibroma transformation, we integrated four human experimental studies and one for mouse, using a gene score-based meta-analysis method, from which we obtained a score-ranked signature of 579 genes. Genes with the highest absolute scores were classified as promising disease biomarkers. By grouping genes with similar neurofibromatosis-related profiles, we derived panels of potential biomarkers. The addition of promoter methylation data to gene profiles indicated a panel of genes probably silenced by hypermethylation. To identify possible therapeutic treatments, we used the gene signature to query drug expression databases. Trichostatin A and other histone deacetylase inhibitors, as well as cantharidin and tamoxifen, were retrieved as putative therapeutic means to reverse the aberrant regulation that drives to malignant cell proliferation and metastasis. This in silico prediction corroborated reported experimental results that suggested the inclusion of these compounds in clinical trials. This experimental validation supported the suitability of the meta-analysis method used to integrate several sources of public genomic information, and the reliability of the gene signature associated to the malignant evolution of neurofibromas to generate working hypotheses for prognostic and drug-responsive biomarkers or therapeutic measures, thus showing the potential of this in silico approach for biomarker discovery.http://europepmc.org/articles/PMC5443557?pdf=render |
| spellingShingle | Marta Martínez Carlos O S Sorzano Alberto Pascual-Montano Jose M Carazo Gene signature associated with benign neurofibroma transformation to malignant peripheral nerve sheath tumors. PLoS ONE |
| title | Gene signature associated with benign neurofibroma transformation to malignant peripheral nerve sheath tumors. |
| title_full | Gene signature associated with benign neurofibroma transformation to malignant peripheral nerve sheath tumors. |
| title_fullStr | Gene signature associated with benign neurofibroma transformation to malignant peripheral nerve sheath tumors. |
| title_full_unstemmed | Gene signature associated with benign neurofibroma transformation to malignant peripheral nerve sheath tumors. |
| title_short | Gene signature associated with benign neurofibroma transformation to malignant peripheral nerve sheath tumors. |
| title_sort | gene signature associated with benign neurofibroma transformation to malignant peripheral nerve sheath tumors |
| url | http://europepmc.org/articles/PMC5443557?pdf=render |
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