Gene expression signature for angiogenic and nonangiogenic non-small-cell lung cancer.
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.
Hu
Jiangting
J
Cancer Research UK Tumour Pathology Group, Nuffield Department of Clinical Laboratory Science, University of Oxford, John Radcliffe Hospital, Headington OX3 9DU, Oxford, UK.
Bianchi
Fabrizio
F
Ferguson
Mary
M
Cesario
Alfredo
A
Margaritora
Stefano
S
Granone
Pierluigi
P
Goldstraw
Peter
P
Tetlow
Michelle
M
Ratcliffe
Cathy
C
Nicholson
Andrew G
AG
Harris
Adrian
A
Gatter
Kevin
K
Pezzella
Francesco
F
D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000235:genetics* / Q000378:metabolism; D015687:Cell Hypoxia; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D013482:Superoxide Dismutase / Q000032:analysis / Q000235:genetics; D000072105:Superoxide Dismutase-1; D019700:Thrombospondin 1 / Q000032:analysis / Q000235:genetics; D014407:Tumor Cells, Cultured
C000606290:SOD1 protein, human; D019700:Thrombospondin 1; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1