The validation of matrix metalloproteinase-9 mRNA gene expression as a predictor of outcome in patients with metastatic gastric cancer
Menée sur des échantillons tumoraux prélevés sur 222 patients atteints d'un cancer gastrique métastatique, cette étude évalue l'association entre le niveau d'expression de l'ARN messager de la métalloprotéinase matricielle 9 et la survie des patients
Background: The prognostic role of matrix metalloproteinase-9 (MMP-9) in metastatic gastric cancer has not been validated.Patients and methods: We carried out a molecular analysis in 222 metastatic gastric cancer patients obtained from clinical trials. We assessed the messenger RNA (mRNA) expression of MMP-9, vascular endothelial growth factor receptor-A, and epidermal growth factor receptor in a training cohort of 130 patients and conducted an independent validation in 92 patients. Automated RNA extraction from paraffin and RT-quantitative PCR was used. Immunohistochemistry for MMP-9 and diverse immune cell infiltrates was conducted.Results: In the training cohort, only MMP-9 significantly correlated with patient's survival. At the cut-off with the highest predictive value, 19% of patients had MMP-9 expression above this cut-off and these showed a median survival of 3.6 months compared with 10.5 months (P = 1.7e−6) in patients with lower expression. Corresponding 1- and 2-year survivals were 9% and 44% and 0 and 21%, respectively. The application of this cut-off to the validation cohort revealed similar distributions of overall survival according to MMP-9 expression on uni- (P < 0.001) and multivariate analyses (P < 0.001). No differences in survival according to MMP-9 below best cut-off were found. MMP-9 protein assessed by immunohistochemistry was not prognostic.Conclusion: MMP-9 mRNA expression above a certain cut-off level is associated with dismal survival.
Annals of Oncology , résumé, 2011