Biological and clinical significance of MMP-2, MMP-9, TIMP-1 and TIMP-2 in non-small cell lung cancer.
Our main aim consists of investigating the clinical usefulness of gelatinases and their tissue inhibitors in non-small cell lung cancer (NSCLC). Thus, we have analysed in 111 NSCLCs, levels and activity of MMP-2, MMP-9, TIMP-1 and TIMP-2, by Enzymoimmunoassay and Gelatine zymography, respectively. Our data revealed higher MMP-2 net activity in the NSCLC population analyzed in this study, this parameter showing a significant association with the TNM stage of tumours (P=0.002). Moreover, MMP-9 levels were significantly associated with poor clinical evolution of patients (P=0.02). Also, disease-free survival time was higher for patients whose tumours showed TIMP-1 increased levels (P=0.04). Of interest, Cox multivariate analysis revealed that TIMP-1 levels can be considered as an independent prognostic factor in NSCLC. Relative Risk (RR) to tumour relapse was more than two times lower for patients showing high TIMP-1 levels (RR=0.420, P=0.041). Therefore, according to our results, we conclude that MMP-9 and TIMP-1 levels of synthesis could be useful for the selection of patients with potentially unfavourable clinical evolution in order to establish adjuvant therapy protocols. Among these parameters, TIMP-1 level evaluation emerges as the main factor to predict the clinical outcome of patients.
Iniesta
Pilar
P
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain.
Morán
Alberto
A
De Juan
Carmen
C
Gómez
Ana
A
Hernando
Florentino
F
García-Aranda
Cristina
C
Frías
Cristina
C
Díaz-López
Antonio
A
Rodríguez-Jiménez
Francisco-Javier
FJ
Balibrea
Jose-Luis
JL
Benito
Manuel
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9