Multi-omics prioritization identifies ISG20 as a candidate molecular target of patulin in colorectal cancer.

Patulin, a mycotoxin commonly found in fruits and fruit products, has been linked to abnormal cell growth and intestinal inflammation, but its relationship to colorectal cancer (CRC) is not well understood. We integrated computational toxicology, transcriptomic analyses across six CRC datasets, WGCNA, target prediction, machine-learning prioritization, single-cell/spatial transcriptomics, docking, and 100-ns molecular dynamics with preliminary EdU and RT-qPCR assays. ProTox 3.0 yielded moderate-confidence predictions. Patulin (0.1 and 0.25 μM) increased EdU incorporation in NCM460 and HCT116 cells, indicating a pro-proliferative effect that was not CRC-specific. Integration identified 20 candidate genes, with exploratory models prioritizing MMP3, GSTP1, and ISG20. At 0.25 μM, MMP3 mRNA increased and ISG20 mRNA decreased in both NCM460 and HCT116 cells, whereas GSTP1 mRNA responses differed between them. Docking generated predicted poses for all three proteins; in 100-ns trajectories, the patulin-ISG20 system showed comparatively lower structural deviation. Transcriptomic analyses associated ISG20 expression with CRC cell populations and immune features, and in silico knockout predicted immune-related transcriptional changes. These results prioritize ISG20 for further investigation. Reduced ISG20 mRNA abundance was measured experimentally, whereas protein depletion, direct binding, catalytic inhibition, and causal immune effects were not established. The transcriptional observations and structural predictions therefore support separate hypotheses rather than a validated mechanism linking patulin to CRC progression. These findings provide a defined starting point for food safety risk assessment of patulin in the colon.