Chih-Yung Chiu1, Tzu-Ping Chen2, Jim-Ray Chen3, Chia-Jung Wang4, Shun-Ying Yin5, Shen-Hao Lai6, Kin-Sun Wong7. 1. Department of Pediatrics, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Pediatric Pulmonology, Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan. 2. Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Thoracic & Cardiovascular Surgery, Chang Gung Memorial Hospital at Keelung, Keelung City, Taiwan. Electronic address: kkl3490@yahoo.com.tw. 3. Department of Pathology, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University, Taoyuan, Taiwan. 4. Department of Pediatrics, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University, Taoyuan, Taiwan. 5. Department of Thoracic & Cardiovascular Surgery, Chang Gung Memorial Hospital at Keelung, Keelung City, Taiwan. 6. Division of Pediatric Pulmonology, Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan. 7. Division of Pediatric Pulmonology, Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: pchest@adm.cgmh.org.tw.
Abstract
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.
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.