Global gene expression profiling of human pleural mesotheliomas: Identification of matrix metalloproteinase 14 (MMP-14) as potential tumour target

Stefania Crispi, Raffaele A. Calogero, Mario Santini, Pasquale Mellone, Bruno Vincenzi, Gennaro Citro, Giovanni Vicidomini, Silvia Fasano, Rosaria Meccariello, Gilda Cobellis, Simona Menegozzo, Riccardo Pierantoni, Francesco Facciolo, Alfonso Baldi, Massimo Menegozzo

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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. Methodology: 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.

Original languageEnglish
Article numbere7016
JournalPLoS One
Volume4
Issue number9
DOIs
Publication statusPublished - Sep 15 2009

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Crispi, S., Calogero, R. A., Santini, M., Mellone, P., Vincenzi, B., Citro, G., Vicidomini, G., Fasano, S., Meccariello, R., Cobellis, G., Menegozzo, S., Pierantoni, R., Facciolo, F., Baldi, A., & Menegozzo, M. (2009). Global gene expression profiling of human pleural mesotheliomas: Identification of matrix metalloproteinase 14 (MMP-14) as potential tumour target. PLoS One, 4(9), [e7016]. https://doi.org/10.1371/journal.pone.0007016