Abstract:

Objective To analyze the predictive value of ferroptosis-related genes for the surgical treatment risk of children with ulcerative colitis (UC). Methods A total of 331 children with UC were selected from the GSE150961 dataset in the GEO database as the research subject. The rectal biopsy specimens were obtained from UC children during diagnostic colonoscopy, and the children followed up for 1 year after diagnosis. Among them, 21 children progressed to colectomy treatment and served as the surgical group, while 310 children served as the non-surgical group. The differentially expressed ferroptosis-related genes in the rectal tissues of the two groups of children were screened out, and their predictive values for the risk of surgical treatment were investigated. Their correlations with immune cell infiltration, inflammatory factors, and genes related to intestinal epithelial barrier function were examined. Results The non-surgical group consisted of 310 cases, including 158 males and 152 females, with an average age of 12.9±3.2 years; the surgical group consisted of 21 cases, including 12 males and 9 females, with an average age of 13.6±2.7 years. Two genes, solute carrier family 7 member 5 (SLC7A5) and Bcl2/adenovirus E1B interacting protein 3 (BNIP3), were screened out as differentially expressed ferroptosis-related genes in the rectal tissues of the two groups of children. Compared with the non-surgical group, the expression levels of SLC7A5 and BNIP3 in the rectal tissues of the surgical group were significantly increased (P<0.001). The results of multivariate Logistic regression analysis showed that SLC7A5 and BNIP3 were risk factors for the progression of UC children to require colectomy treatment (P<0.01). The results of the receiver operating characteristic (ROC) curve showed that the areas under the curve (AUC) of SLC7A5 and BNIP3 in predicting colectomy treatment of children with UC were 0.938 and 0.867, respectively, the AUC of the combined prediction of SLC7A5 and BNIP3 was 0.949 (P<0.05). The results of correlation analysis showed that the levels of SLC7A5 and BNIP3 were positively correlated with the proportions of memory B cells, macrophage M0, and neutrophils (r=0.14-0.47, P<0.05), and negatively correlated with the proportions of naive B cells, resting CD4⁺ memory T cells, regulatory T cells, and macrophage M2 (r=-0.13 to -0.35, P<0.05), and were significantly positively correlated with the expression levels of inflammatory factors CXCL1, CXCL8, TNF, IL1B, TLR2, NLRP3, and IL23A (r=0.12-0.53, P<0.05), and negatively correlated with the levels of genes related to intestinal epithelial barrier function OCLN, TJP1, TJP2, DSG2, CDH1, and MARVELD2 (r=-0.13 to -0.42, P<0.05). Conclusions The expression levels of ferroptosis-related genes SLC7A5 and BNIP3 were increased in the rectal tissues obtained at diagnosis of children with UC requiring colectomy treatment, and they were both risk factors and predictors for colectomy treatment of children with UC.

Key words: ulcerative colitis, children, ferroptosis, surgical treatment, predictive values