Gene Expression Signatures Associated with Pterygium Recurrence.

Background/Objectives: A pterygium is a fibrovascular ocular surface lesion whose recurrence after surgical excision remains a major clinical challenge, yet its molecular determinants of recurrence remain poorly understood. This study investigated transcriptomic profiles of primary pterygium tissue collected at the time of surgery to identify molecular signatures associated with subsequent recurrence. Methods: Eighty-five patients undergoing primary pterygium surgery were enrolled and followed for a mean of 7.32 years. RNA sequencing was performed on primary pterygium tissues collected at the time of surgery. Samples from four pterygia that developed recurrence and four non-recurrent pterygia were studied, with differential expression analyzed using DESeq2 and pathway enrichment via Reactome and GSEA. Results: Recurrence occurred in 5.8% of patients (mean time to recurrence was 8.87 months), exclusively in higher-grade (T2-T3) lesions. Transcriptomic analysis identified 1374 differentially expressed genes (1020 upregulated, 354 downregulated), showing separation between pterygia that developed recurrence from non-recurrent samples. Upregulated genes, including ECM1, HOXB5, MARCO, SHISAL1, CWH43, and PSORS1C1, reflected extracellular matrix remodeling and innate immune pathways, whereas downregulated genes, such as LCN10, ZBTB16, and GPR101, were linked to GPCR signaling and neuronal communication. Samples with the earliest recurrence displayed the most pronounced transcriptomic changes. Conclusions: These findings suggest that extracellular matrix remodeling and innate immunity activation, already present at initial surgery, are associated with subsequent pterygium recurrence and may help in the identification of candidate molecular biomarkers for recurrence risk stratification.