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通过整合 bulk 和单细胞测序数据鉴定溃疡性结肠炎诊断和治疗中的多胺相关生物标志物。

Identifying polyamine related biomarkers in diagnosis and treatment of ulcerative colitis by integrating bulk and single-cell sequencing data.

机构信息

Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Sci Rep. 2024 Aug 5;14(1):18094. doi: 10.1038/s41598-024-69322-6.

DOI:10.1038/s41598-024-69322-6
PMID:39103474
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11300856/
Abstract

Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon, and its pathogenesis remains unclear. Polyamine metabolic enzymes play a crucial role in UC. In this study, we aimed to identify pivotal polyamine-related genes (PRGs) and explore the underlying mechanism between PRGs and the disease status and therapeutic response of UC. We analyzed mRNA-sequencing data and clinical information of UC patients from the GEO database and identified NNMT, PTGS2, TRIM22, TGM2, and PPARG as key PRGs associated with active UC using differential expression analysis and weighted gene co-expression network analysis (WCGNA). Receiver operator characteristic curve (ROC) analysis confirmed the accuracy of these key genes in UC and colitis-associated colon cancer (CAC) diagnosis, and we validated their relationship with therapeutic response in external verification sets. Additionally, single-cell analysis revealed that the key PRGs were specific to certain immune cell types, emphasizing the vital role of intestinal tissue stem cells in active UC. The results were validated in vitro and in vivo experiments, including the colitis mice model and CAC mice model. In conclusion, these key PRGs effectively predict the progression of UC patients and could serve as new pharmacological biomarkers for the therapeutic response of UC.

摘要

溃疡性结肠炎（UC）是一种慢性结肠炎症性疾病，其发病机制尚不清楚。多胺代谢酶在 UC 中起着至关重要的作用。在这项研究中，我们旨在鉴定关键的多胺相关基因（PRGs），并探讨 PRGs 与 UC 的疾病状态和治疗反应之间的潜在机制。我们分析了 GEO 数据库中 UC 患者的 mRNA 测序数据和临床信息，并使用差异表达分析和加权基因共表达网络分析（WCGNA）鉴定出 NNMT、PTGS2、TRIM22、TGM2 和 PPARG 作为与活动期 UC 相关的关键 PRGs。受试者工作特征曲线（ROC）分析证实了这些关键基因在 UC 和结肠炎相关结肠癌（CAC）诊断中的准确性，并在外部验证集中验证了它们与治疗反应的关系。此外，单细胞分析表明关键 PRGs 是特定于某些免疫细胞类型的，强调了肠组织干细胞在活动期 UC 中的重要作用。这些结果在体内和体外实验中得到了验证，包括结肠炎小鼠模型和 CAC 小鼠模型。总之，这些关键 PRGs 可有效预测 UC 患者的病情进展，可作为 UC 治疗反应的新的药理生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/0890d08cca07/41598_2024_69322_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/89217a6f0ab1/41598_2024_69322_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/6c1ed88addc1/41598_2024_69322_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/eb5ea3b3226f/41598_2024_69322_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/9c49b138d690/41598_2024_69322_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/b111a79e87d0/41598_2024_69322_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/85f719424870/41598_2024_69322_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/8eda80256189/41598_2024_69322_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/c5efa14e47da/41598_2024_69322_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/0e1442dbcca3/41598_2024_69322_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/1f7304e76960/41598_2024_69322_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/0890d08cca07/41598_2024_69322_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/89217a6f0ab1/41598_2024_69322_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/6c1ed88addc1/41598_2024_69322_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/eb5ea3b3226f/41598_2024_69322_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/9c49b138d690/41598_2024_69322_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/b111a79e87d0/41598_2024_69322_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/85f719424870/41598_2024_69322_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/8eda80256189/41598_2024_69322_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/c5efa14e47da/41598_2024_69322_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/0e1442dbcca3/41598_2024_69322_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/1f7304e76960/41598_2024_69322_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a637/11300856/0890d08cca07/41598_2024_69322_Fig11_HTML.jpg

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Identifying polyamine related biomarkers in diagnosis and treatment of ulcerative colitis by integrating bulk and single-cell sequencing data.

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[3]
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本文引用的文献

[1]
NNMT-DNMT1 Axis is Essential for Maintaining Cancer Cell Sensitivity to Oxidative Phosphorylation Inhibition.

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[2]
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Proc Natl Acad Sci U S A. 2022-11-8

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Metabolomics. 2022-9-30

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Inhibiting peripheral and central MAO-B ameliorates joint inflammation and cognitive impairment in rheumatoid arthritis.

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Nature. 2022-9

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Global Hospitalization Trends for Crohn's Disease and Ulcerative Colitis in the 21st Century: A Systematic Review With Temporal Analyses.

Clin Gastroenterol Hepatol. 2023-8

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TRIM22 inhibits osteosarcoma progression through destabilizing NRF2 and thus activation of ROS/AMPK/mTOR/autophagy signaling.

Redox Biol. 2022-7

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