A Series of Genes for Predicting Responses to Anti-Tumor Necrosis Factor α Therapy in Crohn's Disease.
A Series of Genes for Predicting Responses to Anti-Tumor Necrosis Factor α Therapy in Crohn's Disease.
复制标题
DOI：
10.3389/fphar.2022.870796
复制
发表时间：
2022
影响因子：
5.6
通讯作者：
Wang, Xiaoyan
中科院分区：
文献类型：
--
作者：
Nie, Kai;Zhang, Chao;Deng, Minzi;Luo, Weiwei;Ma, Kejia;Xu, Jiahao;Wu, Xing;Yang, Yuanyuan;Wang, Xiaoyan
关键词：
背景：克罗恩病（CD）患者的生活质量严重下降，尤其是那些对传统疗法没有反应的患者。抗肿瘤坏死因子（TNF）α通常用作一线治疗；然而，许多患者仍然对这种治疗没有反应，而反应预测因子的识别可以促进治疗策略的改进。 方法：我们筛选了 CD 患者中具有不同抗 TNFα 反应的基因表达综合 (GEO) 微阵列队列（发现队列），并探索了中心基因。这一发现在独立验证队列中得到证实，并进行了多种算法和体外细胞模型以进一步验证核心预测因子。 结果：我们筛选了四个发现数据集。每个队列中均证实了抗 TNFα 应答者和无应答者之间差异表达的基因。基因本体富集揭示了先天免疫参与 CD 患者的抗 TNFα 反应。微阵列的预测分析提供了最小的基因错误分类，并且构建的包含枢纽基因的网络支持TLR2的核心地位。此外，GSEA 还支持 TLR2 作为核心预测器。然后在验证队列中验证最重要的中心基因（GSE159034；p < 0.05）。此外，ROC 分析证明了 TLR2（AUC：0.829）、TREM1（AUC：0.844）和 CXCR1（AUC：0.841）的显着预测价值。此外，单核细胞中的 TLR2 表达影响脂多糖诱导炎症期间的免疫上皮炎症反应和上皮屏障（p < 0.05）。 结论：生物信息学和实验研究确定 TLR2、TREM1、CXCR1、FPR1 和 FPR2 是预测克罗恩病患者抗 TNFα 反应的有希望的候选者，尤其是 TLR2 作为核心预测因子。
Background: Patients with Crohn’s disease (CD) experience severely reduced quality of life, particularly those who do not respond to conventional therapies. Antitumor necrosis factor (TNF)α is commonly used as first-line therapy; however, many patients remain unresponsive to this treatment, and the identification of response predictors could facilitate the improvement of therapeutic strategies. Methods: We screened Gene Expression Omnibus (GEO) microarray cohorts with different anti-TNFα responses in patients with CD (discovery cohort) and explored the hub genes. The finding was confirmed in independent validation cohorts, and multiple algorithms and in vitro cellular models were performed to further validate the core predictor. Results: We screened four discovery datasets. Differentially expressed genes between anti-TNFα responders and nonresponders were confirmed in each cohort. Gene ontology enrichment revealed that innate immunity was involved in the anti-TNFα response in patients with CD. Prediction analysis of microarrays provided the minimum misclassification of genes, and the constructed network containing the hub genes supported the core status of TLR2. Furthermore, GSEA also supports TLR2 as the core predictor. The top hub genes were then validated in the validation cohort (GSE159034; p < 0.05). Furthermore, ROC analyses demonstrated the significant predictive value of TLR2 (AUC: 0.829), TREM1 (AUC: 0.844), and CXCR1 (AUC: 0.841). Moreover, TLR2 expression in monocytes affected the immune–epithelial inflammatory response and epithelial barrier during lipopolysaccharide-induced inflammation (p < 0.05). Conclusion: Bioinformatics and experimental research identified TLR2, TREM1, CXCR1, FPR1, and FPR2 as promising candidates for predicting the anti-TNFα response in patients with Crohn’s disease and especially TLR2 as a core predictor.
登录
查看更多内容
影响因子：
5.8
作者：
Dabney, AR
通讯作者：
Dabney, AR
影响因子：
24.5
作者：
Franco Leal, Raquel;Planell, Nuria;Salas, Azucena
通讯作者：
Salas, Azucena
影响因子：
4.5
作者：
Liu, Yifan;Duan, Yantao;Li, Yousheng
通讯作者：
Li, Yousheng
影响因子：
3.6
作者：
Bravo F;Macpherson JA;Slack E;Patuto N;Cahenzli J;McCoy KD;Macpherson AJ;Juillerat P;SATICC (Sensitivity to Anti-TNF Inhibition in Crohn's disease and ulcerative Colitis) study group
通讯作者：
SATICC (Sensitivity to Anti-TNF Inhibition in Crohn's disease and ulcerative Colitis) study group
影响因子：
7.6
作者：
Bek S;Nielsen JV;Bojesen AB;Franke A;Bank S;Vogel U;Andersen V
通讯作者：
Andersen V