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

循环肿瘤细胞表型的表征可确定部分 EMT 亚群,用于胰腺癌的临床分层

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作者:Alexander Semaan #, Vincent Bernard #, Dong U Kim #, Jaewon J Lee, Jonathan Huang, Nabiollah Kamyabi, Bret M Stephens, Wei Qiao, Gauri R Varadhachary, Matthew H Katz, Yu Shen, Francis Anthony San Lucas, Peter Gascoyne, Hector A Alvarez, Anirban Maitra, Paola A Guerrero1

Background

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

Conclusion

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

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