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预测用于人类溃疡性结肠炎早期诊断和动态严重程度监测的新型生物标志物。

Predicting novel biomarkers for early diagnosis and dynamic severity monitoring of human ulcerative colitis.

作者信息

Chen Yu, Chen Li, Huang Sheng, Yang Li, Wang Li, Yang Feiyun, Huang Jinxiu, Ding Xiuliang

机构信息

Animal Nutrition Institute, Chongqing Academy of Animal Science, Chongqing, China.

Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs, Chongqing, China.

出版信息

Front Genet. 2024 Jul 31;15:1429482. doi: 10.3389/fgene.2024.1429482. eCollection 2024.

DOI:10.3389/fgene.2024.1429482
PMID:39144720
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11321978/
Abstract

BACKGROUND

Ulcerative colitis is an emerging global health concern that poses a significant threat to human health and can progress to colorectal cancer if not diagnosed and treated promptly. Currently, the biomarkers used clinically for diagnosis and dynamic severity monitoring lack disease specificity.

METHODS

Mouse models induced with 2%, 2.5%, and 3% DSS were utilized to simulate human UC with varying severities of inflammation. Transcriptome sequencing technology was employed to identify differentially expressed genes (DEGs) between the control group and each treatment group. Functional enrichment analysis of the KEGG database was performed for shared DEGs among the three treatment groups. DEGs that were significantly and strongly correlated with DSS concentrations were identified using Spearman correlation analysis. Human homologous genes of the interested DEGs were searched in the HomoloGene database, and their regulation patterns in UC patients were validated using the GSE224758 dataset. These genes were then submitted to the DisGeNET database to identify their known associations with human diseases. Online tools, including SignalP 6.0 and DeepTMHMM 1.0, were used to predict signal peptides and transmembrane helices in the amino acid sequences of human genes homologous to the DEGs of interest.

RESULTS

A total of 1,230, 995, and 2,214 DEGs were identified in the 2%, 2.5%, and 3% DSS-induced groups, respectively, with 668 DEGs common across all three groups. These shared DEGs were primarily associated with signaling transport, pathogenesis, and immune response. Through extensive screening, and were identified as potentially novel biomarkers with higher specificity and ease of detection for the early diagnosis and dynamic severity monitoring of human UC, respectively.

CONCLUSION

We have identified two potentially novel biomarkers, and , which are easy of detection and more specific for human UC. These findings provide new insights into the accurate diagnosis and dynamic monitoring of this persistent disease.

摘要

背景

溃疡性结肠炎是一个日益受到全球关注的健康问题,对人类健康构成重大威胁,若不及时诊断和治疗,可能进展为结直肠癌。目前,临床上用于诊断和动态病情监测的生物标志物缺乏疾病特异性。

方法

利用2%、2.5%和3%葡聚糖硫酸钠(DSS)诱导的小鼠模型来模拟不同炎症严重程度的人类溃疡性结肠炎。采用转录组测序技术鉴定对照组与各治疗组之间的差异表达基因(DEG)。对三个治疗组之间的共享DEG进行KEGG数据库的功能富集分析。使用Spearman相关性分析鉴定与DSS浓度显著且强相关的DEG。在同源基因数据库中搜索感兴趣的DEG的人类同源基因,并使用GSE224758数据集验证其在溃疡性结肠炎患者中的调控模式。然后将这些基因提交到DisGeNET数据库,以确定它们与人类疾病的已知关联。使用包括SignalP 6.0和DeepTMHMM 1.0在内的在线工具预测与感兴趣的DEG同源的人类基因氨基酸序列中的信号肽和跨膜螺旋。

结果

在2%、2.5%和3%DSS诱导组中分别鉴定出1230、995和2214个DEG,所有三组共有668个DEG。这些共享的DEG主要与信号转导、发病机制和免疫反应相关。通过广泛筛选,分别鉴定出[具体基因1]和[具体基因2]作为潜在的新型生物标志物,它们对人类溃疡性结肠炎的早期诊断和动态病情监测具有更高的特异性和易于检测性。

结论

我们鉴定出两种潜在的新型生物标志物,[具体基因1]和[具体基因2],它们易于检测且对人类溃疡性结肠炎更具特异性。这些发现为这种持续性疾病的准确诊断和动态监测提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02f/11321978/f17d994b68fb/fgene-15-1429482-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02f/11321978/f12111e65b86/fgene-15-1429482-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02f/11321978/e9b24dd6c5eb/fgene-15-1429482-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02f/11321978/ee02dfcf0d8d/fgene-15-1429482-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02f/11321978/18bd2658d8cd/fgene-15-1429482-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02f/11321978/5d87373876c1/fgene-15-1429482-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02f/11321978/5176ea6a719b/fgene-15-1429482-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02f/11321978/1f572a04e2d4/fgene-15-1429482-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02f/11321978/f17d994b68fb/fgene-15-1429482-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02f/11321978/f12111e65b86/fgene-15-1429482-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02f/11321978/e9b24dd6c5eb/fgene-15-1429482-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02f/11321978/ee02dfcf0d8d/fgene-15-1429482-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02f/11321978/18bd2658d8cd/fgene-15-1429482-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02f/11321978/5d87373876c1/fgene-15-1429482-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02f/11321978/5176ea6a719b/fgene-15-1429482-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02f/11321978/1f572a04e2d4/fgene-15-1429482-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f02f/11321978/f17d994b68fb/fgene-15-1429482-g008.jpg

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