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在液体活检中检测单核细胞中的表位（EDIM），包括鉴定儿童神经母细胞瘤中的 GD2-一项初步研究。

Epitope detection in monocytes (EDIM) for liquid biopsy including identification of GD2 in childhood neuroblastoma-a pilot study.

机构信息

Department of Pediatric Surgery & Pediatric Urology, Children's Hospital, Eberhard-Karls-University Tuebingen, Tuebingen, Germany.

Department of Haematology and Oncology, Children's Hospital, Eberhard-Karls-University Tuebingen, Tuebingen, Germany.

出版信息

Br J Cancer. 2022 Oct;127(7):1324-1331. doi: 10.1038/s41416-022-01855-x. Epub 2022 Jul 21.

DOI:10.1038/s41416-022-01855-x
PMID:35864157
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9519569/
Abstract

BACKGROUND

Neuroblastoma (NB) is the most common paediatric extracranial solid malignancy. We analysed the role of the epitope detection in monocytes (EDIM) technique for liquid biopsy in NB patients.

METHODS

Tumour epitopes transketolase-like 1 (TKTL1), Apo10 (DNaseX) and GD2 were assessed: expression levels in seven NB tumour samples and five NB cell lines were analysed using RT-PCR and flow cytometry. LAN-1 cells were co-cultured with blood and assessed using EDIM. Peripheral blood macrophages of patients with neuroblastoma (n = 38) and healthy individuals (control group, n = 37) were labelled (CD14/CD16) and assessed for TKTL1, Apo10 and GD2 using the EDIM technology.

RESULTS

mRNA expression of TKTL1 and DNaseX/Apo10 was elevated in 6/7 NB samples. Spike experiments showed upregulation of TKTL1, Apo10 and GD2 in LAN-1 cells following co-culturing with blood. TKTL1 and Apo10 were present in macrophages of 36/38 patients, and GD2 in 15/19 patients. The 37 control samples were all negative. EDIM expression scores of the three epitopes allowed differentiation between NB patients and healthy individuals.

CONCLUSIONS

The EDIM test might serve as a non-invasive tool for liquid biopsy in children suffering from NB. Future studies are necessary for assessing risk stratification, tumour biology, treatment monitoring, and early detection of tumour relapses.

摘要

背景

神经母细胞瘤（NB）是最常见的小儿颅外实体恶性肿瘤。我们分析了用于 NB 患者液体活检的表位检测在单核细胞（EDIM）技术的作用。

方法

评估肿瘤表位转酮醇酶样 1（TKTL1）、Apo10（DNaseX）和 GD2：使用 RT-PCR 和流式细胞术分析 7 个 NB 肿瘤样本和 5 个 NB 细胞系中的表达水平。将 LAN-1 细胞与血液共培养并使用 EDIM 进行评估。对 38 名患有神经母细胞瘤的患者（患者组）和 37 名健康个体（对照组）的外周血巨噬细胞进行标记（CD14/CD16），并使用 EDIM 技术评估 TKTL1、Apo10 和 GD2。

结果

6/7 的 NB 样本中 TKTL1 和 DNaseX/Apo10 的 mRNA 表达升高。在与血液共培养后，LAN-1 细胞中 TKTL1、Apo10 和 GD2 的上调显示出 Spike 实验。36/38 名患者的巨噬细胞中存在 TKTL1 和 Apo10，15/19 名患者的巨噬细胞中存在 GD2。37 个对照样本均为阴性。三个表位的 EDIM 表达评分可区分 NB 患者和健康个体。

结论

EDIM 检测可能成为儿童 NB 患者液体活检的一种非侵入性工具。未来的研究有必要评估风险分层、肿瘤生物学、治疗监测和肿瘤复发的早期检测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9494/9519569/c4ec8274b2c7/41416_2022_1855_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9494/9519569/8d3df595dddc/41416_2022_1855_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9494/9519569/c52797201b97/41416_2022_1855_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9494/9519569/90588c655f86/41416_2022_1855_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9494/9519569/27c8de166e0e/41416_2022_1855_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9494/9519569/36db05f08b84/41416_2022_1855_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9494/9519569/c4ec8274b2c7/41416_2022_1855_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9494/9519569/8d3df595dddc/41416_2022_1855_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9494/9519569/c52797201b97/41416_2022_1855_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9494/9519569/90588c655f86/41416_2022_1855_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9494/9519569/27c8de166e0e/41416_2022_1855_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9494/9519569/36db05f08b84/41416_2022_1855_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9494/9519569/c4ec8274b2c7/41416_2022_1855_Fig6_HTML.jpg

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