Identification and validation of GNA15 as a novel diagnostic biomarker in ulcerative colitis
摘要
Despite advances in transcriptomic profiling, reliable diagnostic biomarkers that accurately reflect disease activity and recurrence in ulcerative colitis (UC) remain limited. This study aimed to identify and validate new biomarkers associated with UC. Candidate genes were identified through the intersection analysis of DEGs from the GSE59071 and GSE53306 datasets, weighted gene co-expression network analysis hub genes, and inflammatory response-related genes. Based on this approach, diagnostic biomarkers were selected using least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithms. Diagnostic biomarkers were validated by quantitative real-time polymerase chain reaction, immunohistochemistry, and western blotting. G protein subunit alpha 15 (GNA15) was identified as a new biomarker associated with UC disease activity. Its expression was positively correlated with 24 types of infiltrating immune cells and with the modified Mayo score. GNA15 was upregulated in UC intestinal mucosal samples compared to the control samples. In addition, GNA15 was an independent risk factor associated with UC (odds ratio [OR], 1.225, 95% CI: 1.075–1.397, p = 0.002). The area under the ROC curve for GNA15 protein expression in predicting UC patients was 0.898 (95% CI: 0.786–0.988, p < 0.001). Furthermore, GNA15 expression was significantly increased in dextran sulfate sodium-induced mouse colitis. GNA15 may serve as a new diagnostic biomarker for assessing UC.