Abstract
In this study, we establish a comprehensive bioinformatic and experimental platform for revealing the molecular bases of cadmium (Cd)-induced lung adenocarcinoma (LUAD) and the therapeutic efficacy of the natural polyphenol oxyresveratrol (O-RES) against this disease. A total of 116 differentially expressed genes (DEGs) were obtained, including 30 upregulated and 86 downregulated obtained by integrating five LUAD-related transcriptomic datasets from the GEO database. Results of network analysis identified four core hub genes: upregulated (Mmp9 and Col1a1) and downregulated (Cdh5 and Pecam-1). Using the ToppFUN module, functional enrichment analysis described the identified genes in relevant oncogenic. The in vivo validation with a rat model of Cd-induced lung toxicity further confirmed that the expression levels of these hub genes were markedly changed due to the increased level of Cd, which resembled the human LUAD profile. Strikingly, co-administration of oxyresveratrol (O-RES) further completely abolished the transcriptional aberration of this signaling pathway induced by Cd, indicating that O-RES could attenuate carcinogenic signaling in Cd-induced carcinogenesis. Furthermore, molecular docking analysis revealed that O-RES exhibits strong and specific binding affinities to key LUAD-associated targets, including Mmp9, Col1a1, Cdh5, and Pecam-1, supporting its multi-targeted therapeutic potential. These findings not only underscore the potential of Mmp9, Col1a1, Cdh5, and Pecam-1 as robust biomarkers for Cd-induced LUAD but also highlight O-RES as a promising multi-targeted agent for chemoprevention and therapeutic intervention in environmentally triggered LUAD.