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MicroRNA Signatures in Tumor Tissue Related to Angiogenesis in Non-Small Cell Lung Cancer

BACKGROUND: Angiogenesis is regarded as a hallmark in cancer development, and anti-angiogenic treatment is presently used in non-small cell lung cancer (NSCLC) patients. MicroRNAs (miRs) are small non-coding, endogenous, single stranded RNAs that regulate gene expression. In this study we aimed to i...

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Autores principales: Donnem, Tom, Fenton, Christopher G., Lonvik, Kenneth, Berg, Thomas, Eklo, Katrine, Andersen, Sigve, Stenvold, Helge, Al-Shibli, Khalid, Al-Saad, Samer, Bremnes, Roy M., Busund, Lill-Tove
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266266/
https://www.ncbi.nlm.nih.gov/pubmed/22295063
http://dx.doi.org/10.1371/journal.pone.0029671
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author Donnem, Tom
Fenton, Christopher G.
Lonvik, Kenneth
Berg, Thomas
Eklo, Katrine
Andersen, Sigve
Stenvold, Helge
Al-Shibli, Khalid
Al-Saad, Samer
Bremnes, Roy M.
Busund, Lill-Tove
author_facet Donnem, Tom
Fenton, Christopher G.
Lonvik, Kenneth
Berg, Thomas
Eklo, Katrine
Andersen, Sigve
Stenvold, Helge
Al-Shibli, Khalid
Al-Saad, Samer
Bremnes, Roy M.
Busund, Lill-Tove
author_sort Donnem, Tom
collection PubMed
description BACKGROUND: Angiogenesis is regarded as a hallmark in cancer development, and anti-angiogenic treatment is presently used in non-small cell lung cancer (NSCLC) patients. MicroRNAs (miRs) are small non-coding, endogenous, single stranded RNAs that regulate gene expression. In this study we aimed to identify significantly altered miRs related to angiogenesis in NSCLC. METHODS: From a large cohort of 335 NSCLC patients, paraffin-embedded samples from 10 patients with a short disease specific survival (DSS), 10 with a long DSS and 10 normal controls were analyzed. The miRs were quantified by microarray hybridization and selected miRs were validated by real-time qPCR. The impacts of different pathways, including angiogenesis, were evaluated by Gene Set Enrichment Analysis (GSEA) derived from Protein ANalysis THrough Evolutionary Relationship (PANTHER). One of the most interesting candidate markers, miR-155, was validated by in situ hybridization (ISH) in the total cohort (n = 335) and correlation analyses with several well-known angiogenic markers were done. RESULTS: 128 miRs were significantly up- or down-regulated; normal versus long DSS (n = 68) and/or normal versus short DSS (n = 63) and/or long versus short DSS (n = 37). The pathway analysis indicates angiogenesis-related miRs to be involved in NSCLC. There were strong significant correlations between the array hybridization and qPCR validation data. The significantly altered angiogenesis-related miRs of high interest were miR-21, miR-106a, miR-126, miR-155, miR-182, miR-210 and miR-424. miR-155 correlated significantly with fibroblast growth factor 2 (FGF2) in the total cohort (r = 0.17, P = 0.002), though most prominent in the subgroup with nodal metastasis (r = 0.34, P<0.001). CONCLUSIONS: Several angiogenesis-related miRs are significantly altered in NSCLC. Further studies to understand their biological functions and explore their clinical relevance are warranted.
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spelling pubmed-32662662012-01-31 MicroRNA Signatures in Tumor Tissue Related to Angiogenesis in Non-Small Cell Lung Cancer Donnem, Tom Fenton, Christopher G. Lonvik, Kenneth Berg, Thomas Eklo, Katrine Andersen, Sigve Stenvold, Helge Al-Shibli, Khalid Al-Saad, Samer Bremnes, Roy M. Busund, Lill-Tove PLoS One Research Article BACKGROUND: Angiogenesis is regarded as a hallmark in cancer development, and anti-angiogenic treatment is presently used in non-small cell lung cancer (NSCLC) patients. MicroRNAs (miRs) are small non-coding, endogenous, single stranded RNAs that regulate gene expression. In this study we aimed to identify significantly altered miRs related to angiogenesis in NSCLC. METHODS: From a large cohort of 335 NSCLC patients, paraffin-embedded samples from 10 patients with a short disease specific survival (DSS), 10 with a long DSS and 10 normal controls were analyzed. The miRs were quantified by microarray hybridization and selected miRs were validated by real-time qPCR. The impacts of different pathways, including angiogenesis, were evaluated by Gene Set Enrichment Analysis (GSEA) derived from Protein ANalysis THrough Evolutionary Relationship (PANTHER). One of the most interesting candidate markers, miR-155, was validated by in situ hybridization (ISH) in the total cohort (n = 335) and correlation analyses with several well-known angiogenic markers were done. RESULTS: 128 miRs were significantly up- or down-regulated; normal versus long DSS (n = 68) and/or normal versus short DSS (n = 63) and/or long versus short DSS (n = 37). The pathway analysis indicates angiogenesis-related miRs to be involved in NSCLC. There were strong significant correlations between the array hybridization and qPCR validation data. The significantly altered angiogenesis-related miRs of high interest were miR-21, miR-106a, miR-126, miR-155, miR-182, miR-210 and miR-424. miR-155 correlated significantly with fibroblast growth factor 2 (FGF2) in the total cohort (r = 0.17, P = 0.002), though most prominent in the subgroup with nodal metastasis (r = 0.34, P<0.001). CONCLUSIONS: Several angiogenesis-related miRs are significantly altered in NSCLC. Further studies to understand their biological functions and explore their clinical relevance are warranted. Public Library of Science 2012-01-25 /pmc/articles/PMC3266266/ /pubmed/22295063 http://dx.doi.org/10.1371/journal.pone.0029671 Text en Donnem et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Donnem, Tom
Fenton, Christopher G.
Lonvik, Kenneth
Berg, Thomas
Eklo, Katrine
Andersen, Sigve
Stenvold, Helge
Al-Shibli, Khalid
Al-Saad, Samer
Bremnes, Roy M.
Busund, Lill-Tove
MicroRNA Signatures in Tumor Tissue Related to Angiogenesis in Non-Small Cell Lung Cancer
title MicroRNA Signatures in Tumor Tissue Related to Angiogenesis in Non-Small Cell Lung Cancer
title_full MicroRNA Signatures in Tumor Tissue Related to Angiogenesis in Non-Small Cell Lung Cancer
title_fullStr MicroRNA Signatures in Tumor Tissue Related to Angiogenesis in Non-Small Cell Lung Cancer
title_full_unstemmed MicroRNA Signatures in Tumor Tissue Related to Angiogenesis in Non-Small Cell Lung Cancer
title_short MicroRNA Signatures in Tumor Tissue Related to Angiogenesis in Non-Small Cell Lung Cancer
title_sort microrna signatures in tumor tissue related to angiogenesis in non-small cell lung cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266266/
https://www.ncbi.nlm.nih.gov/pubmed/22295063
http://dx.doi.org/10.1371/journal.pone.0029671
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