Table 2.
Potential liquid-biopsy clinical usefulness in early-diagnosis of pancreatic cancer.
| Study Technique | Specific/Relevant Molecular Findings | Stage | Nº Patients PDAC/Control | Sensitivity (%) | Specificity (%) | Ref. | |
|---|---|---|---|---|---|---|---|
| ctDNA | ctDNA | KRAS mutant allele fraction > 5% | Early PDAC Metastatic |
90/37 104/37 |
34 54 |
NR NR |
[97] |
| Mutations at codons 12, 13 and 61 of KRAS | Early PDAC | 112 | 62 | NR | [95] | ||
| Mutations KRAS exon 2 (codons 12 and 13) | All stages | 52/10 | 65 | 75 | [94] | ||
| KRAS MAFs | All stages | 110/52 | 47 | NR | [96] | ||
| Mutations at codons 12, 13 of KRAS | Early PDAC | 221/182 | 30 | NR | [98] | ||
| Mutations at codons 12, 13 and 61 of KRAS | Early PDAC | 112/76 | 71 | NR | [99] | ||
| ctDNA combined with other serum tumor markers | ctDNA+ CA19.9 | Mutations KRAS exon 2 | All stages | 47/31 | 85-98 | 77-81 | [100] |
| ctDNA+ CA19.9 | KRAS MAFs | All stages | 110/52 | 47 | [96] | ||
| KRAS ctDNA + CEA + CA19.9 + HGF + osteopontin | Mutations at codons 12, 13 of KRAS | Early PDAC | 221/182 | 64 | 99 | [98] | |
| cfDNA methylome | 5-methylcytosine and 5-hydroxymethylcytosine | Global DNA hypomethylation | All stages | 72/136 | 94 | 95 | [101] |
| CTCs | CellSearch® | > 3 CTCs/mL | IPMN PDAC |
21/19 8/19 |
33 73 |
NR | [102] |
| CD45/CEP8/DAPI staining-FISH | CTC detection | PDAC | 95/48 | 76 | 68 | [103] | |
| Anti-EpCAM Portal-vein blood | Number of CTCs in 2 mL portal venous blood (if > 112 indicate hepatic metastasis) | Metastatic Resectable |
17 43 |
100 58 |
NR | [104] | |
| Combined analysis CTC + exosomes | CTC detection and GPC1-positive-exosome detection | Early PDAC | 22/28 | 100 | 80 | [105] | |
| Exosomes | KRAS mutations in exoDNA | Presence mutant KRAS in circulating exosome-derived DNA | Early PDAC Locally advanced Metastatic |
33/54 15/54 20/54 |
67 80 85 |
NR NR NR |
[106] |
| GPC1-exosomes | CTC detection and GPC1-positive-exosome detection | Early PDAC | 22/28 | 50 | 90 | [105] | |
| miRNAs of exosomes | miRNAs in exosomes | All stages | Reported increased expression in PDAC | NR | [107,108,109,110] | ||
| miRNAs | miR-21, miR-25 | miR-21, miR-25 | All stages | 303/760 | 75 | 93 | [111] |
| Meta-analysis | Presence of different miRNAs | All stages | 4,326/4,277 | 79 | 74 | [112] |
ctDNA: circulating tumor DNA; PDAC: pancreatic ductal adenocarcinoma; NR: not reported, CTC: circulating tumor cells; miRNA: micro-RNA; HGF: hepatocyte-growth factor; CEP8: chromosome 8 centromere; FISH: fluorescence in situ hybridization; IPMN: intraductal papillary mucinous neoplasm; EpCAM:epithelial cell adhesion molecule.