Integrated multi-omics analysis reveals shared genetic and immunological biomarkers linking arsenic-induced autophagy to carcinogenesis.

Autophagy is a long-standing biological mechanism that degrades and recycles damaged cellular components. It has become a significant mediator of arsenic poisoning, but its role is complicated and depends on the situation. Chronic inorganic arsenite exposure is a considerable global environmental health issue, strongly linked to multiple cancer types via processes that remain inadequately elucidated. This research employed an integrated multi-omics approach to investigate the molecular network linking inorganic arsenite exposure to cancer progression via disruption of autophagy, examining gene sets associated with cellular responses to inorganic arsenite stress, autophagy (GO:0006914), and cancer-related pathways. We identified a set of 47 essential genes shared by these pathways. The analysis of the protein-protein interaction network identified TP53, MTOR, AKT1, NFKB1, and BECN1 as hub genes, with maximum clique centrality scores of 45, 38, 35, 32, and 28, respectively. Pathway enrichment analysis revealed substantial participation in the PI3K-AKT-mTOR signaling route (p = 2.4e-10), autophagy-animal (p = 5.7e-9), p53 signaling pathway (p = 1.1e-7), and NOD-like receptor signaling pathways (p = 3.2e-6). The visualization results showed several links between genes that respond to inorganic arsenite and the main components of autophagy. Our findings provide a comprehensive molecular framework showing that dysregulation of autophagy is a critical step in inorganic arsenite-induced cancer. This suggests new biomarkers that can be used to identify people who have been exposed to inorganic arsenite early and aid in cancer prevention in those groups.