P699 Identification of A Novel Activated NK-Associated Gene Score Associated with Diagnosis and Biological Therapy Response in Ulcerative Colitis

Abstract

Abstract Background Natural killer (NK) cells are associated with the pathogenesis of ulcerative colitis (UC), while their precise contributions remain unclear. The present study sought to investigate the diagnostic value of activated NK-associated gene score (ANAG score) in UC and evaluate its predictive value in biological therapy response. Methods Bulk RNA-seq datasets were obtained from the Gene Expression Omnibus (GEO). GSE11223, GSE87466, and GSE92415 were integrated for diagnosis value analysis. GSE206285 and GSE92415 were used to analyze the prediction of response to ustekinumab (UST) and golimumab (GLM), respectively. The immune infiltration landscape was estimated by single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. Differentially expressed genes (DEGs) correlated with activated NK cells were identified as activated NK-associated genes (ANAGs). Key ANAGs were screened by protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression. Results The immune infiltration analysis revealed a higher abundance of activated NK cells in non-inflamed UC tissues. 54 DEGs correlated with activated NK cells were identified as ANAGs. PPI analysis and LASSO regression were utilized to screen out 4 key ANAGs (SELP, TIMP1, MMP7, and ABCG2). ANAG score was established with the following formula: ANAG score = 0.628 * SELP + 1.574 * TIMP1 + 0.740 * MMP7 - 0.361 * ABCG2 – 18.940. The ANAG scores were significantly higher in inflamed tissues, as well as in biological therapy non-responders (NR) tissues before treatment. The ANAG score demonstrated excellent diagnostic value (AUC = 0.979). Furthermore, according to quartile stratification, patients with a higher ANAG score before treatment were more likely to experience lack of response to ustekinumab and golimumab. Conclusion This study established a novel ANAG score with the ability to precisely diagnose UC and distinguish the efficacy of biological treatment.