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Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma

The discoidin domain receptors, (DDR)1 and DDR2, have been linked to numerous human cancers. We sought to determine expression levels of DDRs in human lung cancer, investigate prognostic determinates, and determine the prevalence of recently reported mutations in these receptor tyrosine kinases. Tum...

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Autores principales: Ford, C E, Lau, S K, Zhu, C Q, Andersson, T, Tsao, M S, Vogel, W F
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360060/
https://www.ncbi.nlm.nih.gov/pubmed/17299390
http://dx.doi.org/10.1038/sj.bjc.6603614
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author Ford, C E
Lau, S K
Zhu, C Q
Andersson, T
Tsao, M S
Vogel, W F
author_facet Ford, C E
Lau, S K
Zhu, C Q
Andersson, T
Tsao, M S
Vogel, W F
author_sort Ford, C E
collection PubMed
description The discoidin domain receptors, (DDR)1 and DDR2, have been linked to numerous human cancers. We sought to determine expression levels of DDRs in human lung cancer, investigate prognostic determinates, and determine the prevalence of recently reported mutations in these receptor tyrosine kinases. Tumour samples from 146 non-small cell lung carcinoma (NSCLC) patients were analysed for relative expression of DDR1 and DDR2 using quantitative real-time PCR (qRT-PCR). An additional 23 matched tumour and normal tissues were tested for differential expression of DDR1 and DDR2, and previously reported somatic mutations. Discoidin domain receptor 1 was found to be significantly upregulated by 2.15-fold (P=0.0005) and DDR2 significantly downregulated to an equivalent extent (P=0.0001) in tumour vs normal lung tissue. Discoidin domain receptor 2 expression was not predictive for patient survival; however, DDR1 expression was significantly associated with overall (hazard ratio (HR) 0.43, 95% CI=0.22–0.83, P=0.014) and disease-free survival (HR=0.56, 95% CI=0.33–0.94, P=0.029). Multivariate analysis revealed DDR1 is an independent favourable predictor for prognosis independent of tumour differentiation, stage, histology, and patient age. However, contrary to previous work, we did not observe DDR mutations. We conclude that whereas altered expression of DDRs may contribute to malignant progression of NSCLC, it is unlikely that this results from mutations in the DDR1 and DDR2 genes that we investigated.
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spelling pubmed-23600602009-09-10 Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma Ford, C E Lau, S K Zhu, C Q Andersson, T Tsao, M S Vogel, W F Br J Cancer Molecular Diagnostics The discoidin domain receptors, (DDR)1 and DDR2, have been linked to numerous human cancers. We sought to determine expression levels of DDRs in human lung cancer, investigate prognostic determinates, and determine the prevalence of recently reported mutations in these receptor tyrosine kinases. Tumour samples from 146 non-small cell lung carcinoma (NSCLC) patients were analysed for relative expression of DDR1 and DDR2 using quantitative real-time PCR (qRT-PCR). An additional 23 matched tumour and normal tissues were tested for differential expression of DDR1 and DDR2, and previously reported somatic mutations. Discoidin domain receptor 1 was found to be significantly upregulated by 2.15-fold (P=0.0005) and DDR2 significantly downregulated to an equivalent extent (P=0.0001) in tumour vs normal lung tissue. Discoidin domain receptor 2 expression was not predictive for patient survival; however, DDR1 expression was significantly associated with overall (hazard ratio (HR) 0.43, 95% CI=0.22–0.83, P=0.014) and disease-free survival (HR=0.56, 95% CI=0.33–0.94, P=0.029). Multivariate analysis revealed DDR1 is an independent favourable predictor for prognosis independent of tumour differentiation, stage, histology, and patient age. However, contrary to previous work, we did not observe DDR mutations. We conclude that whereas altered expression of DDRs may contribute to malignant progression of NSCLC, it is unlikely that this results from mutations in the DDR1 and DDR2 genes that we investigated. Nature Publishing Group 2007-03-12 2007-02-13 /pmc/articles/PMC2360060/ /pubmed/17299390 http://dx.doi.org/10.1038/sj.bjc.6603614 Text en Copyright © 2007 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Molecular Diagnostics
Ford, C E
Lau, S K
Zhu, C Q
Andersson, T
Tsao, M S
Vogel, W F
Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma
title Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma
title_full Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma
title_fullStr Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma
title_full_unstemmed Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma
title_short Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma
title_sort expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360060/
https://www.ncbi.nlm.nih.gov/pubmed/17299390
http://dx.doi.org/10.1038/sj.bjc.6603614
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