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Table 1��Comparison between biomarkers of pancreatic ductal adenocarcinoma ctDNA
| Target | KRAS, TP53, CDKN2A, SMAD4, BRAF, PIK3CA, ADAMTS1, BNC1, 5MC, H2AZ, H2A1.1, H3K4me2, h2ak119ub | CD45, CEP8, CK, EpCAM |
KRAS, TP53, RNA: miRNA, longRNA Proteins markers: EFGR, EPCAM, MUC-1, GPC-1, WNT2 |
| Isolation | Blood | Blood | Body fluids |
| Tumor information | Epigenetic information | DNA, RNA, Protein | DNA, RNA, Protein |
| Technological approaches | qPCR, dPCR, ddPCR, NGS, commercial kits | Immunoaffinity, Physical methods (size and density) | Density-based, size-based, affinity-based, commercial kits |
| Advantages |
qPCR: Fast and low-cost dPCR: High sensitivity/Specificity NGS: capability to screen for a broad range of genetic variants using high DNA input |
Immunoaffinity: Specific, label-free obtained Physical methods: Fast, simple, Low-cost, label-free obtained |
Density-based: low cost. Independent of marker expression. Size-based: Low-cost, fast, Independent of marker expression. Affinity-based: Specificity. High purity. Commercial kits: Simple, fast. |
| Disadvantages |
General: No early stages qPCR: Low sensitivity. Only points mutations. dPCR: High cost. Only points mutations. NGS: Variable sensitivity. High cost. |
General: Isolation complex and expensive. Technical variability Immunoaffinity: capture only one subpopulation. Low purity. Physical methods: Needs immuno-labeling techniques to distinguish CTCs |
General: Isolation complex by contamination and expensive Density-based: Time, high volume sample, can damage EVs. Size based: contamination. Affinity-based: low sample yield. Commercial kits: High cost. |
| Sensitivity (S) (%) |
34–71% KRAS mutations: codons 12, 13, 61, in different stages. |
73–76% CD45/CEP8 100% Mt, 58% resectable Anti-EpCAM portal vein Blood |
67% ES, 80% LA, 85% Mt KRAS mutations in exoDNA 50% ES GPC1 miRNAs Increased expression |
| Specificity (Sp) (%) |
75–81% Mutations KRAS exon 2 |
68% CD45/CEP8 |
90% ES GPC1 |
| Combined techniques (%) |
S: 85–98%, Sp: 77–81% ctDNA (KRAS exon 2) with CA19.9 S: 47% ctDNA (KRAS MAFs) with CA19.9 |
S: 100%, Sp: 80% CTCs.with EVs |
NR |
| Application |
No suitable for screening of PDAC Monitoring postoperative minimal residual disease Predictor of disease recurrence and prognosis |
Not present in healthy controls Variable sensitivity in early diagnosis Excellent specificity. Follow-up of disease recurrence and prognosis Functional analysis drug resistance |
The highest sensitivity and specificity in early detection Evaluated response of resection or any therapy Biotherapeutic application |
| CTCs | EVs |
|---|
BEAMing: beads-emulsion-amplification-magnetics; CEP8: chromosome 8 centromere; ctDNA: circulating tumor DNA; CTC: circulating tumor cells; dPCR: digital polymerase chain reaction; ddPCR: droplet digital PCR; EpCAM: epithelial cell adhesion molecule; ES: early stages; EVs: extracellular vesicles; GPC1: glypican-1; LA: locally advanced; miRNA: micro-RNA; Mt: metastatic; NGS: next-generation sequencing; NR: not reported.
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10855073/
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