Molecular Biology Underlying COPD and Lung Cancer Converge on FOXM1 Network

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease affecting 4.5 million Canadians. It is also associated with a 10-fold increased risk of lung cancer (LC). The molecular factors leading the progression of COPD to LC are still not completely understood, difficulting the identification of COPD patients at high risk of developing LC. In our study, we investigate the molecular overlap between COPD and LC, aiming to find early actionable features to identify high risk cases in a timely manner. To achieve this, we performed a scan of the entire human genome (instead a priori selection of single potential candidates) to identify a combination of interconnected features (gene networks) correlating with reduced lung function, the gold standard measurement for COPD. To increase the scope of our analysis, we leveraged our in-house data with information generated by collaborators worldwide. As a result, we identified a gene network composed of 31 genes, that are responsible for controlling the rate of cell proliferation. Alterations in this mechanism are one of the hallmarks of tumor development. We then verified that these networks were also altered in lung tumors, indicating that they might participate in malignant transformation. These findings have not been previously described in the context of COPD and LC, which indicates the utility of this novel approach. Additionally, this strategy can be applied to a large number of other diseases. Although more research is needed to establish detailed mechanisms of action of this gene network in COPD, this investigation yielded new mechanisms to be explored in order to counteract the malignant development in patients with COPD.