Identification of dysregulated gene clusters and pathways driving ocular surface squamous neoplasia progression

Ocular Surface Squamous Neoplasia (OSSN) represents a spectrum of ocular malignancies that threaten vision and ocular integrity. To unravel the molecular mechanisms underlying OSSN progression, we conducted RNA-sequencing on conjunctival tissues from healthy individuals and patients with OSSN. Our analysis revealed marked alterations in the expression of genes implicated in inflammation, immune dysregulation, cell cycle regulation, and cellular stress responses. Notably, genes such as TP53, CXCL9, CXCL11, IL6, TNFα, MMP7, MMP9, GSTM1, IFNα, and IL1β showed significant dysregulation in OSSN samples compared to controls. Pathway enrichment analysis highlighted the activation of Interferon-α, Interferon-γ, and IL6/JAK-STAT3 signaling, alongside pathways regulating inflammatory response, p53 signaling, G2M checkpoint, and apical surface integrity. Together, these findings indicate that OSSN is characterized by a pro-inflammatory and proliferative transcriptomic profile driven by chronic immune signaling and disrupted cell cycle control. These findings provide novel insights into the transcriptional landscape of OSSN and identify key pathways that may be targeted for improved diagnosis and therapy. The molecular insights provided by this study can potentially inform stratified management approaches and aid in the development of novel treatments for this challenging ocular surface malignancy.