Genome-Wide Profile of Pleural Mesothelioma versus Parietal and Visceral Pleura: The Emerging Gene Portrait of the Mesothelioma Phenotype
Open Access
- 7 August 2009
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 4 (8), e6554
- https://doi.org/10.1371/journal.pone.0006554
Abstract
Malignant pleural mesothelioma is considered an almost incurable tumour with increasing incidence worldwide. It usually develops in the parietal pleura, from mesothelial lining or submesothelial cells, subsequently invading the visceral pleura. Chromosomal and genomic aberrations of mesothelioma are diverse and heterogenous. Genome-wide profiling of mesothelioma versus parietal and visceral normal pleural tissue could thus reveal novel genes and pathways explaining its aggressive phenotype. Well-characterised tissue from five mesothelioma patients and normal parietal and visceral pleural samples from six non-cancer patients were profiled by Affymetrix oligoarray of 38 500 genes. The lists of differentially expressed genes tested for overrepresentation in KEGG PATHWAYS (Kyoto Encyclopedia of Genes and Genomes) and GO (gene ontology) terms revealed large differences of expression between visceral and parietal pleura, and both tissues differed from mesothelioma. Cell growth and intrinsic resistance in tumour versus parietal pleura was reflected in highly overexpressed cell cycle, mitosis, replication, DNA repair and anti-apoptosis genes. Several genes of the “salvage pathway” that recycle nucleobases were overexpressed, among them TYMS, encoding thymidylate synthase, the main target of the antifolate drug pemetrexed that is active in mesothelioma. Circadian rhythm genes were expressed in favour of tumour growth. The local invasive, non-metastatic phenotype of mesothelioma, could partly be due to overexpression of the known metastasis suppressors NME1 and NME2. Down-regulation of several tumour suppressor genes could contribute to mesothelioma progression. Genes involved in cell communication were down-regulated, indicating that mesothelioma may shield itself from the immune system. Similarly, in non-cancer parietal versus visceral pleura signal transduction, soluble transporter and adhesion genes were down-regulated. This could represent a genetical platform of the parietal pleura propensity to develop mesothelioma. Genome-wide microarray approach using complex human tissue samples revealed novel expression patterns, reflecting some important features of mesothelioma biology that should be further explored.Keywords
This publication has 87 references indexed in Scilit:
- Identification of a prostate cancer susceptibility gene on chromosome 5p13q12 associated with risk of both familial and sporadic diseaseEuropean Journal of Human Genetics, 2008
- Evidence for an Overlapping Role of CLOCK and NPAS2 Transcription Factors in Liver Circadian OscillatorsMolecular and Cellular Biology, 2008
- Mesothelin targeted cancer immunotherapyEuropean Journal Of Cancer, 2008
- KEGG for linking genomes to life and the environmentNucleic Acids Research, 2007
- A framework for significance analysis of gene expression data using dimension reduction methodsBMC Bioinformatics, 2007
- Requirements for Cdk7 in the Assembly of Cdk1/Cyclin B and Activation of Cdk2 Revealed by Chemical Genetics in Human CellsMolecular Cell, 2007
- Global gene expression profiling in human lung cells exposed to cobaltBMC Genomics, 2007
- Cyclin-dependent kinase-1: linking apoptosis to cell cycle and mitotic catastropheCell Death & Differentiation, 2002
- Orc6 Involved in DNA Replication, Chromosome Segregation, and CytokinesisScience, 2002
- Multi-Organ, Multi-Lineage Engraftment by a Single Bone Marrow-Derived Stem CellCell, 2001