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

Ford, Caroline LU ; Lau, S K; Zhu, C Q; Andersson, Tommy LU ; Tsao, M S and Vogel, W F (2007) In British Journal of Cancer 96(5). p.808-814
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
DDR2, DDR1, mutation, lung cancer
in
British Journal of Cancer
volume
96
issue
5
pages
808 - 814
publisher
Nature Publishing Group
external identifiers
  • wos:000244715400020
  • scopus:33847701326
ISSN
1532-1827
DOI
10.1038/sj.bjc.6603614
language
English
LU publication?
yes
id
6328b1db-db05-489a-b633-2b2ddcb416ba (old id 165726)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17299390&dopt=Abstract
date added to LUP
2007-07-24 16:11:55
date last changed
2017-10-22 03:39:33
@article{6328b1db-db05-489a-b633-2b2ddcb416ba,
  abstract     = {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.},
  author       = {Ford, Caroline and Lau, S K and Zhu, C Q and Andersson, Tommy and Tsao, M S and Vogel, W F},
  issn         = {1532-1827},
  keyword      = {DDR2,DDR1,mutation,lung cancer},
  language     = {eng},
  number       = {5},
  pages        = {808--814},
  publisher    = {Nature Publishing Group},
  series       = {British Journal of Cancer},
  title        = {Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma.},
  url          = {http://dx.doi.org/10.1038/sj.bjc.6603614},
  volume       = {96},
  year         = {2007},
}