儿童溃疡性结肠炎手术治疗的预测标志物分析

doi:10.12372/jcp.2025.24e0051

摘要/Abstract

摘要：

目的分析铁死亡相关基因对溃疡性结肠炎（UC）患儿手术治疗风险的预测价值。方法选取GEO数据库数据集GSE150961中331例UC患儿为研究对象，在诊断性结肠镜检查时获取病变直肠组织标本，诊断后随访1年，其中21例患儿进展到施行结肠切除术治疗，作为手术组；310例患儿为非手术组。筛选在两组患儿诊断时获得的病变直肠组织中差异表达的铁死亡相关基因，研究其对UC手术治疗风险的预测价值，以及与免疫细胞浸润、炎症因子、肠道上皮屏障功能相关基因表达的相关性。结果非手术组310例，男158例，女152例，平均年龄（12.9±3.2）岁；手术组21例，男12例，女9例，平均年龄（13.6±2.7）岁。筛选出在两组患儿病变直肠组织中差异表达的铁死亡相关基因2个，包括溶质载体家族7成员5（SLC7A5）和Bcl2/腺病毒E1B相互作用蛋白3（BNIP3）。与非手术组相比，手术组病变直肠组织中SLC7A5和BNIP3表达水平明显升高（P均<0.001）。多因素logistic回归分析表明SLC7A5和BNIP3为UC患儿进展为手术治疗的危险因素（P均<0.01）。受试者工作特征曲线(ROC)结果显示，SLC7A5和BNIP3预测UC患儿手术治疗的曲线下面积（AUC）为0.938和0.867，SLC7A5和BNIP3联合预测的AUC为0.949（P均<0.05）。相关性分析结果表明，SLC7A5和BNIP3表达水平与记忆B细胞、巨噬细胞M0、中性粒细胞比例呈正相关（r=0.14~0.47，P均<0.05），与初始B细胞、静息CD4⁺记忆T细胞、调节性T细胞、巨噬细胞M2比例呈负相关（r=-0.13~-0.35，P均<0.05），与炎症因子CXCL1、CXCL8、TNF、IL1B、TLR2、NLRP3、IL23A表达水平呈显著正相关（r=0.12~0.53，P均<0.05），与肠道上皮屏障功能相关基因OCLN、TJP1、TJP2、DSG2、CDH1、MARVELD2水平呈负相关（r=-0.13~-0.42，P均<0.05）。结论铁死亡相关基因SLC7A5和BNIP3在手术治疗的UC患儿诊断时获取的病变直肠组织中表达水平升高，是UC患儿手术治疗的风险因素和预测因子。

关键词: 溃疡性结肠炎, 儿童, 铁死亡, 手术治疗, 预测价值

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

黄柳芳, 吴博, 王莹. 儿童溃疡性结肠炎手术治疗的预测标志物分析[J]. 临床儿科杂志, 2025, 43(2): 120-127.

HUANG Liufang, WU Bo, WANG Ying. An analysis of predictive markers for surgical treatment of ulcerative colitis in children[J]. Journal of Clinical Pediatrics, 2025, 43(2): 120-127.

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变量	β	标准误	Wald χ²	P	OR值（95%CI)
SLC7A5	1.82	0.41	19.55	<0.001	6.14(2.75~13.73)
BNIP3	1.47	0.49	8.89	0.003	4.34(1.65~11.39)
严重程度	0.32	0.70	0.21	0.651	1.37(0.35~5.39)
常量	-20.58	3.66	31.61	<0.001	-