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细胞焦亡负担与炎症性肠病的抗 TNF 治疗结果相关：生物信息学分析的新见解。

Pyroptosis burden is associated with anti-TNF treatment outcome in inflammatory bowel disease: new insights from bioinformatics analysis.

机构信息

Department of GastroenterologyHebei Key Laboratory of GastroenterologyHebei Clinical Research Center for Digestive Diseases, The Second Hospital of Hebei Medical University, Hebei Institute of Gastroenterology, Shijiazhuang, 050035, Hebei, China.

Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.

出版信息

Sci Rep. 2023 Sep 22;13(1):15821. doi: 10.1038/s41598-023-43091-0.

DOI:10.1038/s41598-023-43091-0
PMID:37740137
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10516897/
Abstract

Biological agents known as anti-tumor necrosis factor (TNF) drugs are frequently utilized in the treatment of inflammatory bowel disease (IBD). In this study, we analyzed the shared processes of pyroptosis in Ulcerative colitis (UC) and Crohn's disease (CD), as well as explored the correlation between the burden of pyroptosis and the results of anti-TNF treatment based on bioinformatics analyses. We identified CAPS1, CASP5, GSDMD, AIM2, and NLRP3 as the hub genes, with AIM2 being the most effective indicator for predicting the response to anti-TNF therapy. We also noticed that non-responders received anti-TNF therapy exhibited elevated AIM2 protein expression. Subsequently, we conducted a cluster analysis based on AIM2-inflammasome-related genes and discovered that patients with a higher burden of AIM2 inflammasome displayed stronger immune function and a poor response to anti-TNF therapy. Overall, our study elucidates the pathway of pyroptosis in IBD and reveals AIM2 expression level as a potential biomarker for predicting the effectiveness of anti-TNF therapy.

摘要

生物制剂，如抗肿瘤坏死因子（TNF）药物，常被用于治疗炎症性肠病（IBD）。本研究通过生物信息学分析，分析了溃疡性结肠炎（UC）和克罗恩病（CD）中细胞焦亡的共同发生过程，并探讨了细胞焦亡负担与抗 TNF 治疗结果之间的相关性。我们确定 CAPS1、CASP5、GSDMD、AIM2 和 NLRP3 为关键基因，其中 AIM2 是预测抗 TNF 治疗反应的最有效指标。我们还注意到，接受抗 TNF 治疗的无应答者 AIM2 蛋白表达升高。随后，我们基于 AIM2-炎症小体相关基因进行聚类分析，发现 AIM2 炎症小体负担较高的患者具有更强的免疫功能和对抗 TNF 治疗的不良反应。总的来说，本研究阐明了 IBD 中细胞焦亡的途径，并揭示了 AIM2 表达水平作为预测抗 TNF 治疗效果的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7396/10516897/12ddfbef3708/41598_2023_43091_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7396/10516897/624c885e46d8/41598_2023_43091_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7396/10516897/12ddfbef3708/41598_2023_43091_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7396/10516897/4ea4a8500425/41598_2023_43091_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7396/10516897/e37af09df9f6/41598_2023_43091_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7396/10516897/e2d2cae6f493/41598_2023_43091_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7396/10516897/6600e9edaf3e/41598_2023_43091_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7396/10516897/62b3753845ed/41598_2023_43091_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7396/10516897/8fabaed28aa2/41598_2023_43091_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7396/10516897/23117dd8e565/41598_2023_43091_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7396/10516897/624c885e46d8/41598_2023_43091_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7396/10516897/12ddfbef3708/41598_2023_43091_Fig9_HTML.jpg

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