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CD27作为诊断生物标志物及其在桥本甲状腺炎免疫异质性和预测临床药物反应中的作用。

CD27 as a Diagnostic Biomarker and Its Role in Immune Heterogeneity and Predicting Clinical Drug Responses in Hashimoto's Thyroiditis.

作者信息

Dong Yan-Ming, Bao Guo-Qiang

机构信息

Department of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi'an, Shaanxi Province, People's Republic of China.

出版信息

Pharmgenomics Pers Med. 2024 Dec 17;17:535-550. doi: 10.2147/PGPM.S487091. eCollection 2024.

DOI:10.2147/PGPM.S487091
PMID:39717528
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11664005/
Abstract

OBJECTIVE

To identify key genes and potential molecular mechanisms associated with Hashimoto's thyroiditis (HT) to provide new insights for the development of diagnostic and therapeutic targets for this disease.

METHODS

Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify the differentially expressed genes (DEGs) associated with HT. A protein-protein interaction (PPI) network was used to obtain hub genes, with CD27 emerging as the key gene in HT. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, Gene Set Enrichment Analysis (GSEA), and HT-infiltrating immune cell components as well as functions were performed to further investigate the role and potential mechanism of CD27 in cohorts with high and low expression of CD27.

RESULTS

CD27 was found to be upregulated in HT tissues and showed considerable clinical utility in HT. The CD27 of the high-expression cohort exhibited a higher enrichment in immune-related biological processes than the low-expression group. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) analysis revealed that several activated HT-infiltrating immune cells were strongly associated with CD27, suggesting that CD27 has the potential to be a marker for the immune state in HT.

CONCLUSION

In our study, CD27 was found to contribute to predicting clinical outcomes in patients with HT, including disease status and response to immunotherapy. CD27 is a promising biomarker for HT microenvironment remodeling, offering insights into new therapeutic approaches to improve treatment of HT.

摘要

目的

鉴定与桥本甲状腺炎(HT)相关的关键基因和潜在分子机制,为该疾病诊断和治疗靶点的开发提供新见解。

方法

进行差异表达分析和加权基因共表达网络分析(WGCNA)以鉴定与HT相关的差异表达基因(DEG)。利用蛋白质-蛋白质相互作用(PPI)网络获得枢纽基因,CD27成为HT中的关键基因。进行基因本体(GO)分析、京都基因与基因组百科全书(KEGG)通路富集分析、基因集富集分析(GSEA)以及HT浸润免疫细胞成分和功能分析,以进一步研究CD27在CD27高表达和低表达队列中的作用及潜在机制。

结果

发现CD27在HT组织中上调,且在HT中具有相当大的临床应用价值。高表达队列的CD27在免疫相关生物学过程中的富集程度高于低表达组。通过估计RNA转录本相对子集进行细胞类型鉴定(CIBERSORT)分析显示,几种活化的HT浸润免疫细胞与CD27密切相关,表明CD27有可能成为HT免疫状态的标志物。

结论

在我们的研究中,发现CD27有助于预测HT患者的临床结局,包括疾病状态和对免疫治疗的反应。CD27是HT微环境重塑的一个有前景的生物标志物,为改善HT治疗的新治疗方法提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4419/11664005/2352ff60e092/PGPM-17-535-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4419/11664005/748954c5875b/PGPM-17-535-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4419/11664005/382f5ecaf7f6/PGPM-17-535-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4419/11664005/527dcb92014c/PGPM-17-535-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4419/11664005/6b926fd6b8fb/PGPM-17-535-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4419/11664005/14c299664e8c/PGPM-17-535-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4419/11664005/0499ed6eb2c8/PGPM-17-535-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4419/11664005/2352ff60e092/PGPM-17-535-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4419/11664005/748954c5875b/PGPM-17-535-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4419/11664005/382f5ecaf7f6/PGPM-17-535-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4419/11664005/527dcb92014c/PGPM-17-535-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4419/11664005/6b926fd6b8fb/PGPM-17-535-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4419/11664005/14c299664e8c/PGPM-17-535-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4419/11664005/0499ed6eb2c8/PGPM-17-535-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4419/11664005/2352ff60e092/PGPM-17-535-g0007.jpg

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本文引用的文献

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Dysregulation of systemic soluble immune checkpoints in early breast cancer is attenuated following administration of neoadjuvant chemotherapy and is associated with recovery of CD27, CD28, CD40, CD80, ICOS and GITR and substantially increased levels of PD-L1, LAG-3 and TIM-3.新辅助化疗后,早期乳腺癌中全身可溶性免疫检查点的失调得到缓解,这与CD27、CD28、CD40、CD80、ICOS和糖皮质激素诱导的肿瘤坏死因子受体(GITR)的恢复以及程序性死亡受体配体1(PD-L1)、淋巴细胞活化基因3(LAG-3)和T细胞免疫球蛋白黏蛋白分子3(TIM-3)水平的显著升高有关。
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