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Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact
Penile carcinoma (PeCa) is an important public health issue in poor and developing countries, and has only recently been explored in terms of genetic and epigenetic studies. Integrative data analysis is a powerful method for the identification of molecular drivers involved in cancer development and...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362487/ https://www.ncbi.nlm.nih.gov/pubmed/28122331 http://dx.doi.org/10.18632/oncotarget.14783 |
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author | Kuasne, Hellen Barros-Filho, Mateus C. Busso-Lopes, Ariane Marchi, Fábio A. Pinheiro, Maisa Muñoz, Juan J. M. Scapulatempo-Neto, Cristovam Faria, Eliney F. Guimarães, Gustavo C. Lopes, Ademar Trindade-Filho, José C. S. Domingues, Maria Aparecida C. Drigo, Sandra A. Rogatto, Silvia R. |
author_facet | Kuasne, Hellen Barros-Filho, Mateus C. Busso-Lopes, Ariane Marchi, Fábio A. Pinheiro, Maisa Muñoz, Juan J. M. Scapulatempo-Neto, Cristovam Faria, Eliney F. Guimarães, Gustavo C. Lopes, Ademar Trindade-Filho, José C. S. Domingues, Maria Aparecida C. Drigo, Sandra A. Rogatto, Silvia R. |
author_sort | Kuasne, Hellen |
collection | PubMed |
description | Penile carcinoma (PeCa) is an important public health issue in poor and developing countries, and has only recently been explored in terms of genetic and epigenetic studies. Integrative data analysis is a powerful method for the identification of molecular drivers involved in cancer development and progression. miRNA and mRNA expression profiles followed by integrative analysis were investigated in 23 PeCa and 12 non-neoplastic penile tissues (NPT). Expression levels of eight miRNAs and 10 mRNAs were evaluated in the same set of samples used for microarray and in a validation set of cases (PeCa = 36; NPT = 27). Eighty-one miRNAs and 2,697 mRNAs were identified as differentially expressed in PeCa. Integrative data analysis revealed 255 mRNAs potentially regulated by 68 miRNAs. Using RT-qPCR, eight miRNAs and nine transcripts were confirmed as altered in PeCa. We identified that MMP1, MMP12 and PPARG and hsa-miR-31-5p, hsa-miR-224-5p, and hsa-miR-223-3p were able to distinguish tumors from NPT with high sensitivity and specificity. Higher MMP1 expression was detected as a better predictor of lymph node metastasis than the clinical-pathological data. In addition, PPARG and EGFR were highlighted as potential pathways for targeted therapy in PeCa. The analysis based on HPV positivity (7 of 23 cases) revealed five miRNA and 13 mRNA differentially expressed. Although in a limited number of cases, HPV positive PeCa presented less aggressive phenotype in comparison with negative cases. Overall, an integrative analysis using mRNA and miRNA profiles revealed markers related with tumor development and progression. Furthermore, MMP1 expression level was a predictive marker for lymph node metastasis in patients with PeCa. |
format | Online Article Text |
id | pubmed-5362487 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53624872017-04-24 Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact Kuasne, Hellen Barros-Filho, Mateus C. Busso-Lopes, Ariane Marchi, Fábio A. Pinheiro, Maisa Muñoz, Juan J. M. Scapulatempo-Neto, Cristovam Faria, Eliney F. Guimarães, Gustavo C. Lopes, Ademar Trindade-Filho, José C. S. Domingues, Maria Aparecida C. Drigo, Sandra A. Rogatto, Silvia R. Oncotarget Research Paper Penile carcinoma (PeCa) is an important public health issue in poor and developing countries, and has only recently been explored in terms of genetic and epigenetic studies. Integrative data analysis is a powerful method for the identification of molecular drivers involved in cancer development and progression. miRNA and mRNA expression profiles followed by integrative analysis were investigated in 23 PeCa and 12 non-neoplastic penile tissues (NPT). Expression levels of eight miRNAs and 10 mRNAs were evaluated in the same set of samples used for microarray and in a validation set of cases (PeCa = 36; NPT = 27). Eighty-one miRNAs and 2,697 mRNAs were identified as differentially expressed in PeCa. Integrative data analysis revealed 255 mRNAs potentially regulated by 68 miRNAs. Using RT-qPCR, eight miRNAs and nine transcripts were confirmed as altered in PeCa. We identified that MMP1, MMP12 and PPARG and hsa-miR-31-5p, hsa-miR-224-5p, and hsa-miR-223-3p were able to distinguish tumors from NPT with high sensitivity and specificity. Higher MMP1 expression was detected as a better predictor of lymph node metastasis than the clinical-pathological data. In addition, PPARG and EGFR were highlighted as potential pathways for targeted therapy in PeCa. The analysis based on HPV positivity (7 of 23 cases) revealed five miRNA and 13 mRNA differentially expressed. Although in a limited number of cases, HPV positive PeCa presented less aggressive phenotype in comparison with negative cases. Overall, an integrative analysis using mRNA and miRNA profiles revealed markers related with tumor development and progression. Furthermore, MMP1 expression level was a predictive marker for lymph node metastasis in patients with PeCa. Impact Journals LLC 2017-01-21 /pmc/articles/PMC5362487/ /pubmed/28122331 http://dx.doi.org/10.18632/oncotarget.14783 Text en Copyright: © 2017 Kuasne et al. http://creativecommons.org/licenses/by/3.0/ 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 Kuasne, Hellen Barros-Filho, Mateus C. Busso-Lopes, Ariane Marchi, Fábio A. Pinheiro, Maisa Muñoz, Juan J. M. Scapulatempo-Neto, Cristovam Faria, Eliney F. Guimarães, Gustavo C. Lopes, Ademar Trindade-Filho, José C. S. Domingues, Maria Aparecida C. Drigo, Sandra A. Rogatto, Silvia R. Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact |
title | Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact |
title_full | Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact |
title_fullStr | Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact |
title_full_unstemmed | Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact |
title_short | Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact |
title_sort | integrative mirna and mrna analysis in penile carcinomas reveals markers and pathways with potential clinical impact |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362487/ https://www.ncbi.nlm.nih.gov/pubmed/28122331 http://dx.doi.org/10.18632/oncotarget.14783 |
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