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循环肿瘤细胞表型特征分析鉴定出胰腺癌临床分层的部分 EMT 亚群。

Characterisation of circulating tumour cell phenotypes identifies a partial-EMT sub-population for clinical stratification of pancreatic cancer.

机构信息

Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

出版信息

Br J Cancer. 2021 Jun;124(12):1970-1977. doi: 10.1038/s41416-021-01350-9. Epub 2021 Mar 30.

DOI:10.1038/s41416-021-01350-9
PMID:33785875
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8185080/
Abstract

BACKGROUND

Limited accessibility of the tumour precludes longitudinal characterisation for therapy guidance in pancreatic ductal adenocarcinoma (PDAC).

METHODS

We utilised dielectrophoresis-field flow fractionation (DEP-FFF) to isolate circulating tumour cells (CTCs) in 272 blood draws from 74 PDAC patients (41 localised, 33 metastatic) to non-invasively monitor disease progression.

RESULTS

Analysis using multiplex imaging flow cytometry revealed four distinct sub-populations of CTCs: epithelial (E-CTC), mesenchymal (M-CTC), partial epithelial-mesenchymal transition (pEMT-CTC) and stem cell-like (SC-CTC). Overall, CTC detection rate was 76.8% (209/272 draws) and total CTC counts did not correlate with any clinicopathological variables. However, the proportion of pEMT-CTCs (prop-pEMT) was correlated with advanced disease, worse progression-free and overall survival in all patients, and earlier recurrence after resection.

CONCLUSION

Our results underscore the importance of immunophenotyping and quantifying specific CTC sub-populations in PDAC.

摘要

背景

由于肿瘤的不可及性,无法对胰腺导管腺癌 (PDAC) 进行纵向特征分析以指导治疗。

方法

我们利用介电泳场流分离 (DEP-FFF) 从 74 名 PDAC 患者 (41 名局限性,33 名转移性) 的 272 份血样中分离循环肿瘤细胞 (CTC),以非侵入性监测疾病进展。

结果

使用多指标成像流式细胞术分析显示 CTC 有四个不同的亚群:上皮 (E-CTC)、间质 (M-CTC)、部分上皮间质转化 (pEMT-CTC) 和干细胞样 (SC-CTC)。总体而言,CTC 的检测率为 76.8%(209/272 次采血),CTC 总数与任何临床病理变量均无相关性。然而,pEMT-CTC 的比例 (prop-pEMT) 与所有患者的晚期疾病、无进展生存期和总生存期较差以及切除后更早复发相关。

结论

我们的结果强调了在 PDAC 中免疫表型分析和定量特定 CTC 亚群的重要性。