Network toxicology and bioinformatics reveal potential molecular links between cadmium exposure and pancreatic cancer

Environmental cadmium (Cd) pollution poses a severe threat to human health due to its strong bioaccumulation and high carcinogenicity. Although Cd exposure has been linked to various cancers, its specific role in pancreatic cancer (PC) remains unclear. This study aimed to explore the molecular mechanisms underlying Cd-associated PC and identify potential diagnostic and therapeutic targets.

Transcriptomic data of PC were obtained from the GEO database to screen differentially expressed genes (DEGs), which were then intersected with Cd-related genes retrieved from the Comparative Toxicogenomics Database (CTD). Functional enrichment analyses, including GO and KEGG, were conducted to identify key biological processes and pathways. Multiple machine learning algorithms were used to construct a diagnostic model and identify hub genes. Furthermore, molecular docking and molecular dynamics simulations were performed to evaluate drug-target interactions, and in vitro experiments were used to validate the effects of Cd exposure on PC cell proliferation and invasiveness.

A total of five key genes-FN1, COL5A1, AHR, COL3A1, and TIMP1-were identified as core regulators of Cd-associated PC. Functional analyses indicated that Cd primarily affects the extracellular matrix (ECM) metabolic and collagen remodeling pathways. Experimental results confirmed that Cd exposure significantly enhanced the proliferation and invasiveness of PC cells. Molecular docking and dynamics simulations revealed that the EGFR inhibitor dacomitinib exhibited favorable predicted binding affinity to FN1, suggesting its potential as a therapeutic agent.

This study reveals that Cd may promote the malignant progression of PC by regulating ECM remodeling through key genes such as FN1. Dacomitinib shows promise as an FN1-associated therapy, offering new insights for the precise prevention and treatment of Cd-associated PC.