ArticleClinical, cosmetic and investigational dermatology2026
Integrative Network Toxicology Identifies NFKB1 and KIF11 as Candidate Genes Associated with 2-Hydroxyphenanthrene in the Context of Psoriasis.
Article in Clinical, cosmetic and investigational dermatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 2-Hydroxyphenanthrene (2-PHE), a polycyclic aromatic hydrocarbon metabolite, has been implicated in immune and inflammatory dysregulation, yet its potential toxicological contribution to psoriasis remains unclear. This study aimed to identify candidate genes and pathways through which 2-PHE might influence psoriasis using a network toxicology framework. Methods: Differentially expressed genes (DEGs) were identified from the psoriasis dataset GSE30999 and intersected with 2-PHE-predicted targets obtained from SEA, SuperPred, and TargetNet. Functional enrichment, protein-protein interaction (PPI) analysis, and topological algorithms were used to define hub genes. Two-sample Mendelian randomization (MR) was performed to explore suggestive associations with psoriasis. Tissue-classification performance was evaluated by ROC analysis in GSE30999 and GSE41662 for distinguishing lesional from non-lesional skin, while GSEA characterized pathway involvement. Molecular docking simulations assessed potential binding modes between 2-PHE and key proteins. Results: A total of 4,185 psoriasis-associated DEGs and 219 2-PHE targets yielded 55 overlapping genes enriched in NF-κB signaling, apoptosis, insulin resistance, and AGE-RAGE pathways. PPI analysis identified 13 hub genes, with NFKB1 and KIF11 showing nominally significant associations with psoriasis in MR analyses. Both NFKB1 and KIF11 showed strong capacity to discriminate lesional from non-lesional tissue and were enriched in inflammatory, immune, and cell-cycle-related pathways. Docking predicted favorable binding energies of 2-PHE to NFKB1 (-5.9 kcal/mol) and KIF11 (-9.0 kcal/mol) in silico. Conclusion: This integrative network toxicology study suggests that NFKB1 and KIF11 are candidate genes potentially involved in the association between 2-PHE and psoriasis, linking environmental exposure to immune activation and cell-cycle dysregulation. However, the genetic evidence remains preliminary, and the lack of colocalization support and the nominal nature of MR findings underscore the need for further validation through functional experiments and larger genetic studies.
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