Spatial heterogeneity in epithelial to mesenchymal transition properties of circulating tumor cells associated with distant recurrence in pancreatic cancer patients
2020 Annals of Translational Medicine. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Annals of translational medicine - 8(2020), 11 vom: 04. Juni, Seite 676 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dong, Xiu [VerfasserIn] |
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| Links: |
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| Themen: |
Circulating tumor cells (CTCs) |
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| Anmerkungen: |
Date Revised 15.04.2022 published: Print Citation Status PubMed-not-MEDLINE |
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| doi: |
10.21037/atm-20-782 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM311950728 |
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| 520 | |a 2020 Annals of Translational Medicine. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Circulating tumor cells (CTCs) | |
| 650 | 4 | |a epithelial to mesenchymal transition (EMT) | |
| 650 | 4 | |a pancreatic cancer (PC) | |
| 650 | 4 | |a prognosis | |
| 650 | 4 | |a spatial heterogeneity | |
| 700 | 1 | |a Ma, Yongsu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xudong |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Xiaodong |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Yulin |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yinmo |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xiaohang |e verfasserin |4 aut | |
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