Overexpression of matrix metalloproteinase-9 in adolescents with primary spontaneous pneumothorax for surgical intervention

Objective: To determine gene expression profiles associated with bullae formation in patients with primary spontaneous pneumothorax and to identify candidate genes associated with surgical intervention. Methods: Twenty-four adolescents with primary spontaneous pneumothorax were enrolled prospectively. A global gene expression analysis of 9 paired lung biopsies (lesion and normal adjacent sites) was performed to identify differentially expressed genes associated with spontaneous pneumothorax. Pathway and network analysis was performed using the Database for Annotation, Visualization and Integrated Discovery web tool. Candidate genes and encoding proteins were assessed in blood samples and compared between patients with pneumothorax and healthy control patients. Results: A total of 1519 differentially expressed transcripts corresponding to known genes were identified comparing the lesion lung with paired adjacent normal lung. The altered genes were mainly associated with focal adhesion and extracellular matrix–receptor interaction pathways. Genes involved in proteolysis and peptidase activity were up-regulated predominantly, especially matrix metalloproteinase-1 and -9 genes. Compared with the recovery stage, blood levels of matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 were increased at the acute stage in patients with pneumothorax and, when compared between patients treated operatively with those treated nonoperatively, were also significantly greater. In addition, ratios of their serum levels were significantly greater in patients with pneumothorax compared with healthy control patients. Furthermore, matrix metalloproteinase-9 was predominantly overexpressed in neutrophils, alveolar macrophages, and mesothelial cells of lung biopsies. Conclusions: An imbalance of cell–extracellular matrix interactions appears to be associated with primary spontaneous pneumothorax. Matrix metalloproteinase-9 overexpression may particularly play a role in contributing to pleural porosity for surgical intervention.