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头颈部鳞状细胞癌治疗反应相关的循环细胞外囊泡和生物标志物的初步研究。

A preliminary investigation of circulating extracellular vesicles and biomarker discovery associated with treatment response in head and neck squamous cell carcinoma.

机构信息

Department of Biological Science, Laboratório de Biologia Molecular do Câncer, UNIFESP, Universidade Federal de São Paulo, Rua Pedro de Toledo, 669 - 11° andar, São Paulo, SP, 04039-032, Brazil.

Cancer Therapeutics Research Laboratory, National Cancer Centre of Singapore, 11 Hospital Drive, Singapore, 169610, Singapore.

出版信息

BMC Cancer. 2019 Apr 23;19(1):373. doi: 10.1186/s12885-019-5565-9.

Abstract

BACKGROUND

There is a paucity of plasma-based biomarkers that prospectively segregate the outcome of patients with head and neck squamous-cell carcinoma (HNSCC) treated with chemoradiation therapy (CRT). Plasma extracellular vesicles (EVs) might be an alternative source for discovery of new specific markers present in patients with HNSCC, which could help to re-direct patients to appropriate curative therapies without delay.

METHODS

In order to identify new markers in plasma compartments, Cholerae toxin B chain (CTB) and Annexin V (AV) were used to isolate EVs from pooled plasma samples from patients with locally advanced HNSCC who responded (CR, n = 6) or presented incomplete response (NR, n = 6) to CRT. The crude plasma and EVs cargo were screened by antibody array.

RESULTS

Of the 370 polypeptides detected, 119 proteins were specific to NR patients while 38 were exclusive of the CR subjects. The Gene Set Enrichment Analysis (GSEA) and Search Tool for the Retrieval of Interacting Genes (STRING) database analysis indicated that the content of circulating plasma EVs might have a relevant function for the tumor intercellular communication in the HNSCC patients.

CONCLUSION

This study provides a list of potential markers present in plasma compartments that might contribute to the development of tools for prediction and assessment of CRT response and potentially guide therapeutic decisions in this context.

摘要

背景

目前缺乏能够前瞻性区分接受放化疗治疗的头颈部鳞状细胞癌(HNSCC)患者结局的基于血浆的生物标志物。血浆细胞外囊泡(EVs)可能是发现 HNSCC 患者中存在的新特异性标志物的另一种来源,这有助于及时将患者重新定向到合适的治愈性治疗方法。

方法

为了鉴定血浆成分中的新标志物,我们使用霍乱毒素 B 链(CTB)和膜联蛋白 V(AV)从对放化疗有反应(CR,n=6)或不完全反应(NR,n=6)的局部晚期 HNSCC 患者的混合血浆样本中分离 EVs。粗血浆和 EVs cargos 通过抗体阵列进行筛选。

结果

在检测到的 370 种多肽中,有 119 种蛋白质是 NR 患者特有的,而 38 种蛋白质是 CR 患者所特有的。基因集富集分析(GSEA)和搜索工具检索相互作用基因(STRING)数据库分析表明,循环血浆 EVs 的内容可能与 HNSCC 患者肿瘤细胞间通讯的相关功能有关。

结论

本研究提供了一组存在于血浆成分中的潜在标志物,这些标志物可能有助于开发预测和评估 CRT 反应的工具,并在这种情况下指导治疗决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ea/6480898/227378bf1169/12885_2019_5565_Fig1_HTML.jpg

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