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基于单细胞RNA测序数据的全面分析,以揭示自然杀伤细胞在甲状腺癌中的潜在分子机制。

A comprehensive analysis to reveal the underlying molecular mechanisms of natural killer cell in thyroid carcinoma based on single-cell RNA sequencing data.

作者信息

Li Xiaoqiong, Wang Kejiang, Liu Jiaxin, Li Yan

机构信息

The Department of Experimental Medicine, Meishan City People's Hospital, No. 288, South Fourth Section, Dongpo Avenue, Meishan, 620000, Sichuan, China.

出版信息

Discov Oncol. 2025 Jan 14;16(1):44. doi: 10.1007/s12672-025-01779-x.

DOI:10.1007/s12672-025-01779-x
PMID:39808350
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11732816/
Abstract

BACKGROUND

Thyroid carcinoma (THCA) is the most common cancer of the endocrine system. Natural killer (NK) cell play an important role in tumor immune surveillance. The aim of this study was to explore the possible molecular mechanisms involved in NK cell in THCA to help the management and treatment of the disease.

METHODS

All data were downloaded from public databases. Candidate hub genes associated with NK cell in THCA were identified by limma, WGCNA and singleR packages. Functional enrichment analysis was performed on the candidate hub genes. Hub genes associated with NK cell were identified by Pearson correlation analysis. The mRNA-miRNA-lncRNA and transcription factors (TF) networks were constructed and the drug was predicted.

RESULTS

The infiltration level of NK cell in THCA tissues was higher than that in paracancerous tissues. KEGG functional enrichment analysis only obtained two signaling pathways, thyroid hormone synthesis and mineral absorption. CTSC, FN1, SLC34A2 and TMSB4X identified by Pearson correlation analysis were considered as the hub genes. Receiver operating characteristic analysis suggested that hub genes may be potential diagnostic biomarkers. In mRNA-miRNA-lncRNA network, FN1 had the highest correlation with IQCH-AS1, and IQCH-AS1 was also correlated with hsa-miR-543. In addition, FN1 and RUNX1 were also found to have the highest correlation in TF network. Finally, NK cell-related drugs belinostat and vorinostat were identified based on ASGARD.

CONCLUSION

The identification of important signaling pathways, molecules and drugs provides potential research directions for further research in THCA and contributes to the development of diagnostic and therapeutic approaches for this disease.

摘要

背景

甲状腺癌(THCA)是内分泌系统最常见的癌症。自然杀伤(NK)细胞在肿瘤免疫监视中发挥重要作用。本研究旨在探讨THCA中NK细胞相关的可能分子机制,以辅助该疾病的管理和治疗。

方法

所有数据均从公共数据库下载。通过limma、WGCNA和singleR软件包鉴定与THCA中NK细胞相关的候选枢纽基因。对候选枢纽基因进行功能富集分析。通过Pearson相关分析鉴定与NK细胞相关的枢纽基因。构建mRNA-miRNA-lncRNA和转录因子(TF)网络并预测药物。

结果

THCA组织中NK细胞的浸润水平高于癌旁组织。KEGG功能富集分析仅获得两条信号通路,即甲状腺激素合成和矿物质吸收。通过Pearson相关分析鉴定的CTSC、FN1、SLC34A2和TMSB4X被视为枢纽基因。受试者工作特征分析表明,枢纽基因可能是潜在的诊断生物标志物。在mRNA-miRNA-lncRNA网络中,FN1与IQCH-AS1的相关性最高,且IQCH-AS1也与hsa-miR-543相关。此外,在TF网络中还发现FN1和RUNX1的相关性最高。最后,基于ASGARD鉴定出与NK细胞相关的药物贝利司他和伏立诺他。

结论

重要信号通路、分子和药物的鉴定为THCA的进一步研究提供了潜在的研究方向,并有助于该疾病诊断和治疗方法的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2f/11732816/5f9211f76bf0/12672_2025_1779_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2f/11732816/5f9211f76bf0/12672_2025_1779_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2f/11732816/5ccd049ffbbf/12672_2025_1779_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2f/11732816/7c2120523d65/12672_2025_1779_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2f/11732816/48b2c01b05eb/12672_2025_1779_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2f/11732816/a3342b49f4db/12672_2025_1779_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2f/11732816/aedc82c3b999/12672_2025_1779_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2f/11732816/5f9211f76bf0/12672_2025_1779_Fig7_HTML.jpg

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