Endoplasmic reticulum stress-related genes contribute to lung cancer risk: a multiomics data integration study

Background: The role of endoplasmic reticulum stress (ERS) in lung cancer remains inadequately explored, with existing studies reporting conflicting results. This study aimed to investigate the causal relationships between ERS-related genes and lung cancer risk. Methods: This study used two large-scale genome-wide association studies (GWAS) datasets on lung cancer and integrated multiomics data, including methylation, expression and protein quantitative trait loci, to determine the causal relationships between methylation, gene expression, protein abundance, and lung cancer risk via summary data-based Mendelian randomization (SMR) and colocalization analyses. The findings revealed regulatory effects of methylation on gene and protein expression. Moreover, using cancer databases, key genes and proteins with prognostic significance were validated, and their correlations with immune cell infiltration within the tumor microenvironment were examined. Results: : HR =1.17, 95% CI: 1.01-1.36]. Conclusions: may contribute to increased lung cancer risk and be associated with poor prognosis in affected patients.