Abstract
Angiogenesis is regarded as essential for tumour growth. However, we have demonstrated that some other aggressive non-small-cell lung carcinomas (n-SCLC) do not have angiogenesis. In this study, using cDNA microarray analysis, we demonstrate that angiogenic and nonangiogenic tumour types can be distinguished by their gene expression profiles. Tissue samples from 42 n-SCLC patients were obtained with consent. In all, 12 tumours were nonangiogenic and 30 angiogenic. The two groups were matched by age, sex, smoking and tumour stage. Total RNAs were extracted followed by microarray hybridization and image scan procedure. Data were analysed using GeneSpring 5.1 software. A total of 62 genes were found to be able to separate angiogenic from nonangiogenic tumours. Nonangiogenic tumours have higher levels of genes concerned with mitochondrial metabolism, mRNA transcription, protein synthesis and the cell cycle. Angiogenic tumours have higher levels of genes coding for membrane vesicles, integrins, remodelling, angiogenesis and apoptosis. These results further support our first finding that nonangiogenic lung tumours are fast-growing tumours filling the alveoli in the absence of vascular remodelling. We raise the hypothesis that in nonangiogenic tumours, hypoxia leads to a higher activation of the mitochondrial respiratory chain, which allows tumour growth without triggering angiogenesis.
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Acknowledgements
We thank Miss Leticia Campo, Mrs Helen Turley and Dr Russel Leek for their help with immunostaining and some of the data analysis. We also thank Julian Downward, John Sgourous and Simon Tomlinson (Cancer Research UK, Lincoln's Inn Field, London) for their continuous support, and Doug Altman, Russel Leek, Domenico Delia and Ugo Pastorino for discussing the manuscript. This work was supported by Cancer Research UK and, in part, by the European Union Funded TuBaFrost Consortium. The microarray consortium is funded by the Welcome Trust, Cancer Research UK and the Ludwig Institute of Cancer Research. We thank the staff of the Sanger Institute Microarray Facility (http://www.sanger.ac.uk/Projects/Microarrays) for the supply of arrays, lab protocols and technical advice (David Vetrie, Cordelia Langford, Adam Whittaker, Neil Sutton), Quantarray/GeneSpring datafiles and all data analysis and databases related to elements on the arrays (Kate Rice, Rob Andrews, Adam Butler, Harish Chudasama). The human IMAGE cDNA collection was obtained from the MRC HGMP Resource Centre (Hinxton, UK). All cDNA clone resequencing was performed by Team 56 at the Sanger Institute.
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Hu, J., Bianchi, F., Ferguson, M. et al. Gene expression signature for angiogenic and nonangiogenic non-small-cell lung cancer. Oncogene 24, 1212–1219 (2005). https://doi.org/10.1038/sj.onc.1208242
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DOI: https://doi.org/10.1038/sj.onc.1208242
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