title: Global gene expression profiling of human pleural mesotheliomas: identification of matrix metalloproteinase 14 (MMP-14) as potential tumour target.
abstract: BACKGROUND
  The goal of our study was to molecularly dissect mesothelioma tumour pathways by mean of microarray technologies in order to identify new tumour biomarkers that could be used as early diagnostic markers and possibly as specific molecular therapeutic targets.
  
  
  METHODS
  We performed Affymetrix HGU133A plus 2.0 microarray analysis, containing probes for about 39,000 human transcripts, comparing 9 human pleural mesotheliomas with 4 normal pleural specimens. Stringent statistical feature selection detected a set of differentially expressed genes that have been further evaluated to identify potential biomarkers to be used in early diagnostics. Selected genes were confirmed by RT-PCR. As reported by other mesothelioma profiling studies, most of genes are involved in G2/M transition. Our list contains several genes previously described as prognostic classifier. Furthermore, we found novel genes, never associated before to mesotheliom that could be involved in tumour progression. Notable is the identification of MMP-14, a member of matrix metalloproteinase family. In a cohort of 70 mesothelioma patients, we found by a multivariate Cox regression analysis, that the only parameter influencing overall survival was expression of MMP14. The calculated relative risk of death in MM patients with low MMP14 expression was significantly lower than patients with high MMp14 expression (P = 0.002).
  
  
  CONCLUSIONS
  Based on the results provided, this molecule could be viewed as a new and effective therapeutic target to test for the cure of mesothelioma.
authors.affiliation: Gene Expression Core, Human Molecular Genetics Laboratory, Institute of Genetics and Biophysics, Naples, Italy. crispi@igb.cnr.it
authors.forename: Stefania
authors.initials: S
authors.lastname: Crispi
authors.forename: Raffaele A
authors.initials: RA
authors.lastname: Calogero
authors.forename: Mario
authors.initials: M
authors.lastname: Santini
authors.forename: Pasquale
authors.initials: P
authors.lastname: Mellone
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Gennaro
authors.initials: G
authors.lastname: Citro
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vicidomini
authors.forename: Silvia
authors.initials: S
authors.lastname: Fasano
authors.forename: Rosaria
authors.initials: R
authors.lastname: Meccariello
authors.forename: Gilda
authors.initials: G
authors.lastname: Cobellis
authors.forename: Simona
authors.initials: S
authors.lastname: Menegozzo
authors.forename: Riccardo
authors.initials: R
authors.lastname: Pierantoni
authors.forename: Francesco
authors.initials: F
authors.lastname: Facciolo
authors.forename: Alfonso
authors.initials: A
authors.lastname: Baldi
authors.forename: Massimo
authors.initials: M
authors.lastname: Menegozzo
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor; D002453:Cell Cycle; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000235:genetics* / Q000378:metabolism; D008654:Mesothelioma / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010997:Pleural Neoplasms / Q000235:genetics* / Q000378:metabolism; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk
chemical_list: D014408:Biomarkers, Tumor; D053511:Matrix Metalloproteinase 14