期刊
ANNALS OF TRANSLATIONAL MEDICINE
卷 8, 期 11, 页码 -出版社
AME PUBLISHING COMPANY
DOI: 10.21037/atm-20-782
关键词
Circulating tumor cells (CTCs); epithelial to mesenchymal transition (EMT); pancreatic cancer (PC); prognosis; spatial heterogeneity
资金
- National Key R&D Program of China [2018YFC1313101, 2017ZX10203205-003-001, 2016YGC0901403]
- National Natural Science Foundation of China [81872033, 81871954]
- CAMS Innovation Fund for Medical Sciences [2019-I2M-1-003, 2016-I2M-1-001, 2017-I2M-3-005]
- Youth Clinical Research Project of Peking University First Hospital [2019CR18]
Background: The spatial heterogeneity of epithelial to mesenchymal transition (EMT)-related circulating tumor cells (CTCs) within the circulatory system and its potential clinical relevance remain unclear in pancreatic cancer (PC) patients. We aimed to map the distribution of EMT-related CTCs along the spreading pathway and investigate the prognostic significance due to the potential spatial heterogeneity in the count and phenotypic properties of CTCs. Methods: Both portal vein (PoV) and peripheral vein (PV) blood samples were collected from 39 PC patients. CTCs were isolated by using a CD45 negative enrichment method, and EMT-related phenotypes in CTCs were analyzed by 4-channel immunofluorescence. The correlations of CTCs with patient characteristics and recurrence-free survival (RFS) were analyzed. Results: Both the number {median CTC total count, 10 [6-16] in PoV vs. 5 [1-7] in PV per mL, P<0.0001} and EMT status of CTCs [median mesenchymal CTC (M-CTC) percentage, 0.33 (0.13-0.52) in PoV vs. 0.2 (0-0.4) in PV, P=0.0211] showed significant spatial heterogeneity during dissemination from the PoV to the PV. Univariate analysis adjusting for patient age and sex revealed that CTC total count and M-CTC percentage in PoV samples could be risk factors for RFS in PC patients (P=0.003 and P=0.001, respectively), and ROC curve analysis found that both of these factors had good performance in distinguishing patients with early distant recurrence (within 6 months), with the optimal cut-off values of 14 cells/mL (AUROC = 0.893, sensitivity = 0.857, specificity = 0.813, P=0.001) and 0.545 (AUROC = 0.795, sensitivity = 0.714, specificity = 0.906, P=0.016), respectively. Conclusions: Multivascular assessment of EMT-related CTCs suggested profound dynamic alterations in total count and phenotypes during dissemination, and the spatial heterogeneity of CTCs in circulation could help establish novel prognosis markers in PC patients.
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