Exploring dysregulation of cuproptosis-related genes molecular clusters and candidate biomarkers in pterygium

Pterygium is a common ocular surface disorder, with its prevalence strongly correlated to ultraviolet (UV) exposure in geographic regions. Epidemiological investigations reveal significant demographic variations, with higher incidences observed in areas with intense UV radiation and within specific populations, notably rural individuals. Despite surgical interventions being the standard treatment, recurrent cases underline the necessity for understanding the underlying biological mechanisms contributing to pterygium pathogenesis. Recent advancements in cellular death mechanisms point to cuproptosis, a copper-dependent programmed cell death pathway, as a potential regulatory factor in ocular diseases, including pterygium. This study aims to systematically investigate the immunological significance of cuproptosis-related genes (CuRGs) in pterygium's pathogenesis using an integrative bioinformatics framework. We performed transcriptomic profiling on pterygium tissues and employed machine learning algorithms to identify pivotal biomarkers for pterygium risk stratification. Comprehensive immune profiling and functional enrichment analyses were conducted to elucidate the interplay between identified CuRGs and the immune microenvironment in pterygium. Our analysis highlighted 19 CuRGs, with eight genes displaying significant dysregulation in pterygium tissues (p < 0.05). We established robust associations between CuRG expression and prominent immune cell infiltrates, notably regulatory T cells and macrophages. Furthermore, three core biomarkers (SERTAD1, JMJD1C, CSRNP1) were identified through machine learning and validated by QPCR, with the support vector machine model demonstrating exceptional predictive performance (AUC = 0.84). Empirical validation corroborated significant downregulation of selected biomarkers in pterygium tissue samples compared to normal conjunctiva. Our findings underscore the vital role of CuRGs in modulating pterygium development through immune and metabolic interactions, establishing their potential as novel therapeutic targets. Nevertheless, our study has limitations, as these findings are hypothesis-generating and require validation in larger patient cohorts.