Cargando…
Integrative miRNA-Gene Expression Analysis Enables Refinement of Associated Biology and Prediction of Response to Cetuximab in Head and Neck Squamous Cell Cancer
This paper documents the process by which we, through gene and miRNA expression profiling of the same samples of head and neck squamous cell carcinomas (HNSCC) and an integrative miRNA-mRNA expression analysis, were able to identify candidate biomarkers of progression-free survival (PFS) in patients...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295029/ https://www.ncbi.nlm.nih.gov/pubmed/28098823 http://dx.doi.org/10.3390/genes8010035 |
_version_ | 1782505350208946176 |
---|---|
author | De Cecco, Loris Giannoccaro, Marco Marchesi, Edoardo Bossi, Paolo Favales, Federica Locati, Laura D. Licitra, Lisa Pilotti, Silvana Canevari, Silvana |
author_facet | De Cecco, Loris Giannoccaro, Marco Marchesi, Edoardo Bossi, Paolo Favales, Federica Locati, Laura D. Licitra, Lisa Pilotti, Silvana Canevari, Silvana |
author_sort | De Cecco, Loris |
collection | PubMed |
description | This paper documents the process by which we, through gene and miRNA expression profiling of the same samples of head and neck squamous cell carcinomas (HNSCC) and an integrative miRNA-mRNA expression analysis, were able to identify candidate biomarkers of progression-free survival (PFS) in patients treated with cetuximab-based approaches. Through sparse partial least square–discriminant analysis (sPLS-DA) and supervised analysis, 36 miRNAs were identified in two components that clearly separated long- and short-PFS patients. Gene set enrichment analysis identified a significant correlation between the miRNA first-component and EGFR signaling, keratinocyte differentiation, and p53. Another significant correlation was identified between the second component and RAS, NOTCH, immune/inflammatory response, epithelial–mesenchymal transition (EMT), and angiogenesis pathways. Regularized canonical correlation analysis of sPLS-DA miRNA and gene data combined with the MAGIA2 web-tool highlighted 16 miRNAs and 84 genes that were interconnected in a total of 245 interactions. After feature selection by a smoothed t-statistic support vector machine, we identified three miRNAs and five genes in the miRNA-gene network whose expression result was the most relevant in predicting PFS (Area Under the Curve, AUC = 0.992). Overall, using a well-defined clinical setting and up-to-date bioinformatics tools, we are able to give the proof of principle that an integrative miRNA-mRNA expression could greatly contribute to the refinement of the biology behind a predictive model. |
format | Online Article Text |
id | pubmed-5295029 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-52950292017-02-10 Integrative miRNA-Gene Expression Analysis Enables Refinement of Associated Biology and Prediction of Response to Cetuximab in Head and Neck Squamous Cell Cancer De Cecco, Loris Giannoccaro, Marco Marchesi, Edoardo Bossi, Paolo Favales, Federica Locati, Laura D. Licitra, Lisa Pilotti, Silvana Canevari, Silvana Genes (Basel) Article This paper documents the process by which we, through gene and miRNA expression profiling of the same samples of head and neck squamous cell carcinomas (HNSCC) and an integrative miRNA-mRNA expression analysis, were able to identify candidate biomarkers of progression-free survival (PFS) in patients treated with cetuximab-based approaches. Through sparse partial least square–discriminant analysis (sPLS-DA) and supervised analysis, 36 miRNAs were identified in two components that clearly separated long- and short-PFS patients. Gene set enrichment analysis identified a significant correlation between the miRNA first-component and EGFR signaling, keratinocyte differentiation, and p53. Another significant correlation was identified between the second component and RAS, NOTCH, immune/inflammatory response, epithelial–mesenchymal transition (EMT), and angiogenesis pathways. Regularized canonical correlation analysis of sPLS-DA miRNA and gene data combined with the MAGIA2 web-tool highlighted 16 miRNAs and 84 genes that were interconnected in a total of 245 interactions. After feature selection by a smoothed t-statistic support vector machine, we identified three miRNAs and five genes in the miRNA-gene network whose expression result was the most relevant in predicting PFS (Area Under the Curve, AUC = 0.992). Overall, using a well-defined clinical setting and up-to-date bioinformatics tools, we are able to give the proof of principle that an integrative miRNA-mRNA expression could greatly contribute to the refinement of the biology behind a predictive model. MDPI 2017-01-14 /pmc/articles/PMC5295029/ /pubmed/28098823 http://dx.doi.org/10.3390/genes8010035 Text en © 2017 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 De Cecco, Loris Giannoccaro, Marco Marchesi, Edoardo Bossi, Paolo Favales, Federica Locati, Laura D. Licitra, Lisa Pilotti, Silvana Canevari, Silvana Integrative miRNA-Gene Expression Analysis Enables Refinement of Associated Biology and Prediction of Response to Cetuximab in Head and Neck Squamous Cell Cancer |
title | Integrative miRNA-Gene Expression Analysis Enables Refinement of Associated Biology and Prediction of Response to Cetuximab in Head and Neck Squamous Cell Cancer |
title_full | Integrative miRNA-Gene Expression Analysis Enables Refinement of Associated Biology and Prediction of Response to Cetuximab in Head and Neck Squamous Cell Cancer |
title_fullStr | Integrative miRNA-Gene Expression Analysis Enables Refinement of Associated Biology and Prediction of Response to Cetuximab in Head and Neck Squamous Cell Cancer |
title_full_unstemmed | Integrative miRNA-Gene Expression Analysis Enables Refinement of Associated Biology and Prediction of Response to Cetuximab in Head and Neck Squamous Cell Cancer |
title_short | Integrative miRNA-Gene Expression Analysis Enables Refinement of Associated Biology and Prediction of Response to Cetuximab in Head and Neck Squamous Cell Cancer |
title_sort | integrative mirna-gene expression analysis enables refinement of associated biology and prediction of response to cetuximab in head and neck squamous cell cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295029/ https://www.ncbi.nlm.nih.gov/pubmed/28098823 http://dx.doi.org/10.3390/genes8010035 |
work_keys_str_mv | AT dececcoloris integrativemirnageneexpressionanalysisenablesrefinementofassociatedbiologyandpredictionofresponsetocetuximabinheadandnecksquamouscellcancer AT giannoccaromarco integrativemirnageneexpressionanalysisenablesrefinementofassociatedbiologyandpredictionofresponsetocetuximabinheadandnecksquamouscellcancer AT marchesiedoardo integrativemirnageneexpressionanalysisenablesrefinementofassociatedbiologyandpredictionofresponsetocetuximabinheadandnecksquamouscellcancer AT bossipaolo integrativemirnageneexpressionanalysisenablesrefinementofassociatedbiologyandpredictionofresponsetocetuximabinheadandnecksquamouscellcancer AT favalesfederica integrativemirnageneexpressionanalysisenablesrefinementofassociatedbiologyandpredictionofresponsetocetuximabinheadandnecksquamouscellcancer AT locatilaurad integrativemirnageneexpressionanalysisenablesrefinementofassociatedbiologyandpredictionofresponsetocetuximabinheadandnecksquamouscellcancer AT licitralisa integrativemirnageneexpressionanalysisenablesrefinementofassociatedbiologyandpredictionofresponsetocetuximabinheadandnecksquamouscellcancer AT pilottisilvana integrativemirnageneexpressionanalysisenablesrefinementofassociatedbiologyandpredictionofresponsetocetuximabinheadandnecksquamouscellcancer AT canevarisilvana integrativemirnageneexpressionanalysisenablesrefinementofassociatedbiologyandpredictionofresponsetocetuximabinheadandnecksquamouscellcancer |