Global gene expression profiling of human pleural mesotheliomas: identification of matrix metalloproteinase 14 (MMP-14) as potential tumour target.
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.
Crispi
Stefania
S
Gene Expression Core, Human Molecular Genetics Laboratory, Institute of Genetics and Biophysics, Naples, Italy. crispi@igb.cnr.it
Calogero
Raffaele A
RA
Santini
Mario
M
Mellone
Pasquale
P
Vincenzi
Bruno
B
Citro
Gennaro
G
Vicidomini
Giovanni
G
Fasano
Silvia
S
Meccariello
Rosaria
R
Cobellis
Gilda
G
Menegozzo
Simona
S
Pierantoni
Riccardo
R
Facciolo
Francesco
F
Baldi
Alfonso
A
Menegozzo
Massimo
M
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
D014408:Biomarkers, Tumor; D053511:Matrix Metalloproteinase 14