Grant: Travel Awards - Institute Community Support

Rationale: Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death globally, increases the risk of developing lung cancer by six times, independent of smoking history. While the exact mechanisms linking COPD and lung cancer remain unclear, evidence suggests a direct relationship between the severity of COPD and increased lung cancer risk. This led us to investigate two key questions: Are there molecular changes in severe COPD patients that drive lung cancer development, and can these changes help identify high-risk patients? Approach: We analyzed lung tissue samples from 267 patients divided into four groups: individuals with COPD, without COPD, and COPD patients with and without lung cancer. This analysis was conducted using advanced computational techniques. Findings: We discovered a unique group of 31 genes that are highly active in patients with both severe COPD and lung cancer. 28 of these genes are significantly more active in lung cancer tissue compared to non-cancerous lung tissue. We also found that 21 of the 31 genes play key roles in two interconnected processes: mitosis (the way cells divide) and DNA repair (the way cells fix damage to their genetic material). Additionally, these genes often show changes in their structure, such as missing or extra copies (called deletions and amplifications) or mutations that can disrupt their normal function. Further analysis of larger samples from patients with COPD and lung cancer revealed additional evidence of cellular abnormalities linked to higher lung cancer risk and more severe COPD. Impact: Our findings provide molecular evidence that repetitive tissue injury and repair caused by COPD-related DNA damage, inflammation, and smoking contribute to lung cancer development. This research highlights the potential for identifying COPD patients at higher risk for lung cancer, paving the way for targeted prevention, early detection, and personalized treatment strategies.