Ai-assisted Integrative Transcriptomic Analysis Supports Mechanistic Delineation Of Nodular And Extensive Keloid Subtypes With Therapeutic Implications

BACKGROUND

Keloids are heterogeneous fibrotic skin disorders in which nodular and extensive forms differ in growth behavior, recurrence, and treatment response. While transcriptomic studies have identified subtype-specific signatures, the mechanistic architectures underlying these divergent phenotypes remain unresolved.

OBJECTIVE

To achieve a system-level dissection of nodular and extensive keloids to support subtype-adapted treatment using AI-assisted transcriptomic analysis.

METHODS

We reanalyzed published transcriptomic data from primary dermal fibroblasts of nodular, extensive keloids and healthy skin using OCEAN (Omics-to-Clinical Evidence & Action Navigator), an AI-assisted framework integrating differential expression, pathway enrichment, and protein–protein interaction networks into coherent mechanistic architectures with traceable evidence. Cultured fibroblasts from normal skin biopsies or extensive/nodular keloids were used for biological experiments aimed to validate IA underlined pathways and new pharmacological target molecules.

RESULTS

AI-assisted analysis confirmed known subtype differences, including a dominant extracellular matrix program in nodular keloids and a more inflammatory profile
in extensive keloids. System-level integration reconstructed distinct mechanistic
architectures: nodular keloids displayed a compact, self-reinforcing fibrotic network integrating TGF-β signaling, hypoxia adaptation, transcriptional stabilization, and autocrine inflammation, consistent with reduced therapeutic responsiveness. In contrast, extensive keloids showed an adaptive, expansion-oriented program marked by immune responsiveness, stromal plasticity, angiogenic signaling, and metabolic stress adaptation, revealing subtype-specific therapeutic vulnerabilities.

CONCLUSION

AI-assisted integrative transcriptomics transforms descriptive omics profiles into clinically actionable mechanistic insight, enabling precision stratification and mechanism-informed therapeutic targeting in keloid disease.