GPR97 is a novel diagnostic biomarker and immunomodulatory target in ulcerative colitis: evidence from integrated bioinformatics and experimental validation

Objective Ulcerative colitis (UC) is a chronic relapsing non-specific intestinal inflammatory disorder lacking highly specific early diagnostic biomarkers. This study aimed to identify immune-related hub genes in UC via integrated bioinformatics and experimental validation, and evaluate their diagnostic value for early UC diagnosis and pathogenesis research. Methods Transcriptomic datasets of UC peripheral blood and intestinal tissues were obtained from the GEO database. Differentially expressed genes (DEGs) were screened, and UC-associated core module genes were identified via WGCNA. Immune-related core genes were acquired by intersecting DEGs, WGCNA core genes and integrated public immune gene sets. Hub genes were filtered via machine learning, validated in independent datasets for expression consistency and diagnostic performance, and analyzed for correlation with immune cell infiltration. A mouse colitis model and clinical colon biopsies were used to verify hub gene expression and changes after sulfasalazine (SASP) treatment. Results Three candidate hub genes ( ADGRG3 / GPR97 , P2RY10 , CEP290 ) were identified. Only GPR97 was stably upregulated in both UC blood and intestinal tissues, with all area under the curve (AUC) values above 0.8 and optimal diagnostic efficacy. GPR97 expression significantly correlated with infiltration of plasma cells, CD4+ memory T cells and M0 macrophages. GPR97 was markedly elevated in UC blood and colon tissues, and significantly downregulated after SASP intervention, with favorable disease discrimination capacity. Conclusion GPR97 is stably upregulated in UC and closely linked to intestinal immune dysregulation. It may serve as a promising diagnostic biomarker and immunomodulatory target, providing novel evidence for UC pathogenesis elucidation and clinical precision management.