The Role of Tumor Necrosis Factor Receptor Binding in Linking Non-Small Cell Lung Cancer and Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) and lung cancer (LC) are both primarily associated with smoking and share a complex and not fully understood relationship. Current hypotheses propose that cigarette smoke induces oxidative stress and sustained inflammation, creating an environment conducive to the development of both conditions. Additionally, the repeated cycles of injury and repair characteristic of COPD may play a role in the initiation of tumorigenesis. This study aims to elucidate the molecular mechanisms that facilitate the transition from COPD to lung cancer through in-silico analyses. The Gene Expression Omnibus and NCBI-Sequence Read Archive (NCBI-SRA) were explored to identify relevant studies involving human subjects with Non-Small Cell Lung Cancer (NSCLC) and COPD. This careful selection process culminated in the inclusion of 18 BioProjects focused on NSCLC and 7 BioProjects focused on COPD, as detailed in Supplementary Table 1A. To ensure the quality and relevance of the data, the inclusion criteria were established as follows: i) all BioProjects must feature transcriptomic expression data derived from Next-Generation Sequencing (NGS), and ii) the selected projects must provide both diseased (NSCLC or COPD) and healthy control primary lung samples from humans. Additionally, to maintain the integrity of the analysis, datasets that involved drug or chemotherapy treatments, as well as those exhibiting comorbidities, were deliberately excluded. Using transcriptomic data from patients and control groups, differential gene expression analysis, enriched pathway analysis, and network analysis were conducted. The Tumor Necrosis Factor (TNF) pathway associated genes (along with other pathway associated genes) shows similar expression regulation pattern in both NSCLC and COPD groups as compared to their control. Our findings suggest that the TNF (pro-inflammatory cytokine) pathway, may serve as a critical link between COPD and NSCLC.