Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma.
(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:
https://lup.lub.lu.se/record/165726
- author
- Ford, Caroline LU ; Lau, S K ; Zhu, C Q ; Andersson, Tommy LU ; Tsao, M S and Vogel, W F
- organization
- publishing date
- 2007
- 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
- pmid:17299390
- 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
- 2016-04-01 11:50:52
- date last changed
- 2022-04-05 05:55:46
@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}}, keywords = {{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}}, doi = {{10.1038/sj.bjc.6603614}}, volume = {{96}}, year = {{2007}}, }