High Clinical Value of Liquid Biopsy to Detect Circulating Tumor Cells and Tumor Exosomes in Pancreatic Ductal Adenocarcinoma Patients Eligible for Up-Front Surgery
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Surgical Procedure, Blood Sampling, and Tumor Staging
2.3. CTC Identification
2.4. CRISPR/Cas9-Driven Cut of KRAS Wild-Type (WT) Allele
2.5. Exosome Analysis
2.6. Statistics
3. Results
3.1. Cohort Characteristics
3.2. Cell Spiking Experiments
3.3. Diagnostic Values of CTC or GPC1+-Exosome Detection in Peripheral and Portal Blood
3.4. Diagnostic Value of Combined Diagnosis Methods
3.5. Liquid Biopsy and Prognostic Performances
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Variables | PDAC Group (n = 22) n (%) | IPMN (n = 8) n (%) |
---|---|---|
Procedures | ||
Whipple | 20 (91) | 7 (87) |
Left pancreatectomy | 2 (9) | 1 (13) |
Vascular reconstruction | 4 (18) | 0 (0) |
Post-operative complications | ||
Dindo-Clavien III–IV | 3 (13) | 2 (25) |
Dindo-Clavien V | 0 (0) | 0 (0) |
Pathology: Macroscopic | ||
Tumor size (mm) mean (med; range) | 31 (30; 11–49) | In situ carcinoma n = 0 (0) High grade dysplasia n = 6 (75) Low grade dysplasia n = 2 (25) |
Tumor stage | ||
Stage 1a | 1 (4.5) | |
Stage 1b | 4 (18) | |
Stage 2b | 11 (50) | |
Stage 3 | 6 (27.5) | |
Nodes status | ||
Positive | 17 (77.5) | |
Negative | 5 (22.5) | |
Glandular Differentiation | ||
Well | 3 (13.5) | |
Moderately | 11 (50) | |
Poorly | 8 (36.5) | |
KRAS status: all primary tumors were positive for KRAS mean mutant allele frequency (med; range) | 26.15 (17.45; 0.35–77.6) |
Test | Sensitivity (95% CI) | Specificity (95% CI) | Positive Predictive Value (95% CI) | Negative Predictive Value (95% CI) | Diagnosis Accuracy (95% CI) | |
---|---|---|---|---|---|---|
Conventional tools | ||||||
CA19-9 | 37 (19–59) | 87 (72–95) | 63 (36–85) | 69 (54–82) | 68 (61–74) | |
EUS FNA (n = 18; PDAC n = 15; IPMN n = 3) | 60 (36–81) | 100 (31–99) | 100 (60–99) | 33 (13–65) | 66 (59–73) | |
Single biomarker based diagnosis method in liquid biopsy | ||||||
CTCs | CellSearch® peripheral and/or portal vein (n = 30) | 32 (15–49) | 100 | 100 | 35 (18–52) | 50 (32–68) |
RosetteSepTM portal vein (n = 30) | 46 (28–64) | 75 (59–90) | 84 (71–97) | 34 (17–51) | 54 (36–72) | |
RosetteSepTM peripheral vein (n = 42) | 50 (35–65) | 90 (81–99) | 85 (74–96) | 63 (48–78) | 70 (56–84) | |
RosetteSepTM peripheral and/or portal vein (n = 52) | 59 (46–72) | 87 (78–96) | 77 (66–88) | 75 (63–87) | 75 (63–87) | |
EVs | EVs GPC1 portal vein | 46 (27–66) | 88 (53–99) | 91 (63–99) | 36 (20–59) | 57 (50–64) |
EVs GPC1 peripheral vein | 50 (31–70) | 90 (77–99) | 79 (58–98) | 70 (54–82) | 72 (65–78) | |
EVs GPC1 peripheral and/or portal vein | 64 (43–81) | 90 (73–97) | 83 (59–94) | 76 (59–88) | 78 (72–83) | |
Combined diagnosis methods | ||||||
CA19-9 and EUS-FNA | 50 (31–70) | 92 (78–99) | 86 (58–98) | 70 (55–83) | 74 (67–80) | |
* CTC RosetteSepTM + EVs GPC1 | 96 (90–100) | 70 (55–83) | 70 (55–83) | 96 (90–100) | 81 (70–93) | |
* CTC RosetteSepTM + CA19-9 + * EVs GPC1 | 96 (90–100) | 68 (54–83) | 68 (54–83) | 96 (90–100) | 79 (67–92) | |
* CTC RosetteSepTM + * EVs GPC1 + EUS FNA | 96 (90–100) | 70 (55–83) | 70 (55–83) | 96 (90–100) | 81 (70–93) | |
* CTC RosetteSepTM + CA19-9 + * EVs GPC1 + EUS FNA | 96 (90–100) | 68 (54–83) | 68 (54–83) | 96 (90–100) | 79 (67–92) | |
* CTC CellSearch® + * CTC RosetteSepTM + * EVs GPC1 | 100 | 80 (68–93) | 85 (75–96) | 100 | 91 (83–99) |
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Buscail, E.; Alix-Panabières, C.; Quincy, P.; Cauvin, T.; Chauvet, A.; Degrandi, O.; Caumont, C.; Verdon, S.; Lamrissi, I.; Moranvillier, I.; et al. High Clinical Value of Liquid Biopsy to Detect Circulating Tumor Cells and Tumor Exosomes in Pancreatic Ductal Adenocarcinoma Patients Eligible for Up-Front Surgery. Cancers 2019, 11, 1656. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11111656
Buscail E, Alix-Panabières C, Quincy P, Cauvin T, Chauvet A, Degrandi O, Caumont C, Verdon S, Lamrissi I, Moranvillier I, et al. High Clinical Value of Liquid Biopsy to Detect Circulating Tumor Cells and Tumor Exosomes in Pancreatic Ductal Adenocarcinoma Patients Eligible for Up-Front Surgery. Cancers. 2019; 11(11):1656. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11111656
Chicago/Turabian StyleBuscail, Etienne, Catherine Alix-Panabières, Pascaline Quincy, Thomas Cauvin, Alexandre Chauvet, Olivier Degrandi, Charline Caumont, Séverine Verdon, Isabelle Lamrissi, Isabelle Moranvillier, and et al. 2019. "High Clinical Value of Liquid Biopsy to Detect Circulating Tumor Cells and Tumor Exosomes in Pancreatic Ductal Adenocarcinoma Patients Eligible for Up-Front Surgery" Cancers 11, no. 11: 1656. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11111656