Table 1.
Biomarker Name | Biomarker Type | Single or Multi-Study Validated | Platform | Sample Type | Sample Size (Total Number Patients) | Sensitivity (95% Confidence Interval) | Specificity (95% Confidence Interval) | P-Value | Purpose | References |
---|---|---|---|---|---|---|---|---|---|---|
KRAS and/OR GNAS | Genetic mutation panel | Multi | PCR | Cyst fluid | 91 | 65% | 100% (83–100) | N/A | MCN vs. non-MCN | [38] |
(52–76) | 98% | |||||||||
84% | (86–100) | N/A | IPMN vs. non-IPMN | |||||||
(70–92) | ||||||||||
95.50% | ||||||||||
PCR using NGS | Cyst fluid | 197 | 68.50% | (N/A) | N/A | IPMN vs. non-IPMN | [39] | |||
(N/A) | ||||||||||
100% | ||||||||||
NGS | Cyst fluid | 595 | 89% | (88–100) | N/A | MCN vs. non-MCN | [40] | |||
(79–95) | 100% | |||||||||
Sanger sequencing | Cyst fluid | 159 | 65% | (N/A) | N/A | MCN vs. non-MCN | ||||
(N/A) | ||||||||||
lncRNA-TFG | Long noncoding RNA | Single | Affymetrix human exon 1.0 ST | Tissue | 28 | N/A | N/A | 6.23 × 10−8 | Positive correlation with tumorigenesis in IPMNs | [41] |
CTD-2033D15.2 | Long non-coding RNA | Single | Affymetrix human exon 1.0 ST | Tissue | 28 | N/A | N/A | 1.47 × 10−4 | Negative correlation with tumorigenesis in IPMNs | [41] |
HAND2-AS1 | Long non-coding RNA | Single | Affymetrix human exon 1.0 ST | Tissue | 28 | N/A | N/A | 2.66 × 10−3 | Negative correlation with tumorigenesis in IPMNs | [41] |
Glucose | Metabolite | Multi | Liquid chromatography | Cyst fluid | 19 | 94% | 64% | 0.004 | Glucose ≤ 66 mg/dL in MCNs vs. non-MCNs | [42] |
(N/A) | (N/A) | |||||||||
Glucometer | Glucose ≤ 50 mg/dL in MCNs vs. non-MCNs | |||||||||
Cyst fluid | 153 | 92% | 87% | N/A | [43] | |||||
(N/A) | (N/A) | |||||||||
Kynurenine | Metabolite | Single | Liquid chromatography | Cyst fluid | 19 | 90% | 100% | 0.002 | Lower in MCNs vs. non-MCNs | [42] |
(N/A) | (N/A) | |||||||||
AcSperm and | Metabolite panel | Single | Mass spectrometry | Blood plasma | 121 | 66.70% | 95% | N/A | PDAC vs. N | [44] |
DAS and | (N/A) | (N/A) | ||||||||
LPC(18: 0) and LPC(20: 3) and indole derivative | ||||||||||
ADAMTS1 | Methylated gene | Single | Methylation on beads | Blood cfDNA | 39 | 87.20% | 95.80% | N/A | PDAC vs. N | [45] |
(N/A) | (N/A) | |||||||||
BNC1 | Methylated gene | Single | Methylation on beads | Blood cfDNA | 39 | 64.10% | 93.70% | N/A | PDAC vs. N | [45] |
(N/A) | (N/A) | |||||||||
SOX17 | Methylated gene | Single | Methylation-specific ddPCR | Cyst fluid | 154 | 78.40% | 85.60% | N/A | High-risk PCL vs. low-risk PCLs | [46] |
(64.7–88.7) | (78.4–91.1) | |||||||||
TBX15 and BMP3 | Methylated gene marker panel | Single | Whole-genome methylome discovery and qPCR | Cyst fluid | 134 | 90% | 92% | N/A | HGD/PC vs. LGD/N | [47] |
(70–99) | (85–96) | |||||||||
ADAMTS1 and/OR BNC1 | Methylated gene panel | Single | Methylation on beads | Blood cfDNA | 39 | 97.40% | 91.60% | N/A | PDAC vs. N | [45] |
(N/A) | (N/A) | |||||||||
FOXE1 and SLIT2 and | Methylated gene panel | Single | Methylation-specific ddPCR | Cyst fluid | 154 | 84.30% | 89.40% | N/A | High-risk PCL vs. low-risk PCLs | [46] |
EYA4 and SFRP1 | (N/A) | (N/A) | ||||||||
miR-1290 | MicroRNA | Multi | MicroRNA array analysis | Blood serum | 60 | 88% | 84% | N/A | PC vs. N | [48] |
(N/A) | (N/A) | |||||||||
76 | 83% | 69% | N/A | PC vs. CP | ||||||
(N/A) | (N/A) | |||||||||
95 | 83% | 78% | N/A | PC vs. CP and N | ||||||
(N/A) | (N/A) | |||||||||
qRT-PCR | Blood plasma | |||||||||
49 | N/A | N/A | 0.027 | PDAC vs. N | [49] | |||||
Blood serum | ||||||||||
qRT-PCR | ||||||||||
200 | 74.20% | 91.20% | N/A | PC vs. C | [50] | |||||
(N/A) | (N/A) | |||||||||
9-miRNA model a | MicroRNA panel | Single | TaqMan miRNA Array | Tissue and | 33 and 50 | 89% | 100% | N/A | HG IPMNs, PanNETs and SPNs vs. LG IPMNs and SCAs | [51] |
cyst fluid | (N/A) | (N/A) | ||||||||
miR-3679-5p and miR-940 | MicroRNA panel | Single | qPCR | Saliva | 80 | 72.50% | 70.00% | N/A | PC vs. N | [52] |
(N/A) | (N/A) | |||||||||
60 | 62.50% | 80.00% | N/A | PC vs. BPT | ||||||
(N/A) | (N/A) | |||||||||
100 | 70.00% | 70.00% | N/A | PC vs. N and BPT | ||||||
(N/A) | (N/A) | |||||||||
CA19-9 | Protein- | Multi | Bead-based xMAP immunoassay | Blood serum | 267 | 57.20% | 90% | N/A | PDAC vs. N | [53] |
associated | (N/A) | (N/A) | ||||||||
ELISA | ||||||||||
Blood plasma | ||||||||||
176 | 77.50% | 83.10% | N/A | CA19-9 >20.3 U/mL | [54] | |||||
Retrospective clinical data | Blood serum | (N/A) | (N/A) | PDAC vs. C | ||||||
41 | 90% | 83.33% | N/A | 2.45 times elevated CA19-9 indicated recurrence of PC | [55] | |||||
(N/A) | (N/A) | |||||||||
CEA | Protein | Multi | Clinical data | Cyst fluid | 31 | 73% | 89% | N/A | CEA > 192 ;ng/mL for MCN | [42] |
(N/A) | (N/A) | |||||||||
ELISA | Cyst fluid | 149 | 95.50% | 81.50% | <0.0001 | CEA ≤ 10 ng/mL for SCN | [56] | |||
(N/A) | (N/A) | |||||||||
Enzyme-linked immunosorbent assay | Cyst fluid | 153 | 58% | 96% | N/A | CEA > 192 ng/mL for MC | [43] | |||
(N/A) | (N/A) | |||||||||
MUC5AC:WGA and MUC5AC:BGH and Endorepellin:WGA | Protein | Multi | Antibody-lectin sandwich microarray | Cyst fluid | 147 | 92% b | 94% b | N/A | Elevation in any two differentiates MCNs vs. non-MCNs | [57] |
panel | (N/A) | (N/A) | ||||||||
Antibody-lectin sandwich arrays | Elevation in any two differentiates MCNs vs. non-MCNs | |||||||||
Cyst fluid | 22 | 87% | 100% | N/A | [58] | |||||
(N/A) | (N/A) | |||||||||
Thymosin- β4 | Protein | Single | MALDI imaging and mass spectrometry | Tissue | 45 | 70% | 71% | 0.011 | Overexpressed in IPMN with HGD | [59] |
(N/A) | (N/A) | |||||||||
Ubiquitin | Protein | Single | MALDI imaging and mass spectrometry | Tissue | 45 | 94% | 86% | 0.04 | Overexpressed in IPMN with HGD | [59] |
(N/A) | (N/A) | |||||||||
VEGF-A | Protein | Single | ELISA | Cyst fluid | 149 | 100% | 83.70% | <0.0001 | VEGF-A > 5000 pg/mL benign SCN | [56] |
(N/A) | (N/A) | |||||||||
VEGF-A and CEA | Protein panel | Single | ELISA | Cyst fluid | 149 | 95.50% | 100% | N/A | VEGF-A > 5000 pg/mL and CEA ≤ 10 ng/mL in benign SCN | [56] |
(N/A) | (N/A) |
BPT = benign pancreatic tumour, C = non-cancer control, CP = chronic pancreatitis, ELISA = enzyme-linked immunosorbent assay, HG = high grade, HGD = high-grade dysplasia, IPMN = intraductal papillary mucinous neoplasm, LG = low grade, LGD = low-grade dysplasia, MALDI = matrix-assisted laser desorption ionisation, MC = mucinous cyst, MCN = mucinous cystic neoplasm, N = normal healthy, N/A = not available, NGS = next-generation sequencing, PanNET = pancreatic neuroendocrine tumour, PC = pancreatic cancer, PCL = pancreatic cystic lesion, PCR = polymerase chain reaction, PDAC = pancreatic ductal adenocarcinoma, SCN = serous cystic neoplasm, and SPN = solid-pseudopapillary neoplasm. a Model is intellectual property of the authors. b Average of three cohorts.