Table 2.
Study | Country | study design | Cases vs Controls | Specimen | Stage | Status Controls | Detection Method | markers | SEN% | SPE% | AUC | P Value | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Number | Age | Male (%) | ||||||||||||
MPs | ||||||||||||||
Melo, 2015 [30] | Germany | Case–control | 5/126 | / | / | Serum | 0-I | NCb | Flow cytometry | GPC1 | 100 | 100 | 1.00 | / |
18/126 | / | / | Serum | IIa | Flow cytometry | GPC1 | 100 | 100 | 1.00 | / | ||||
117/126 | / | / | Serum | IIb | Flow cytometry | GPC1 | 100 | 100 | 1.00 | / | ||||
11/126 | / | / | Serum | III | Flow cytometry | GPC1 | 100 | 100 | 1.00 | / | ||||
41/126 | / | / | Serum | IV | Flow cytometry | GPC1 | 100 | 100 | 1.00 | / | ||||
Case–control | 56/26 | 70/NA | 50/NA | Serum | I-IV | Flow cytometry | GPC1 | 100 | 100 | 1.00 | / | |||
Liang, 2017 [34] a | USA | Case–control | 49/48 | NA/62 | NA/40 | Plasma | I-III | HC | nPES assay | EphA2 | 94 | 85 | 0.96 | < 0.001 |
49/48 | NA/52 | NA/52 | Plasma | I-III | CP | nPES assay | EphA2 | 89 | 85 | 0.94 | < 0.001 | |||
37/48 | 67/62 | 60/40 | Plasma | I-II | HC | nPES assay | EphA2 | 91 | 85 | 0.96 | < 0.001 | |||
37/48 | 67/52 | 60/52 | Plasma | I-II | CP | nPES assay | EphA2 | 86 | 85 | 0.93 | < 0.001 | |||
Yang, 2017 [47]a | USA | Prospective | 22/21 | / | / | plasma | / | NCc | NPS chip | GPC1 | 82 | 52 | / | / |
EGFR | 59 | 76 | / | / | ||||||||||
EPCAM | 45 | 95 | / | / | ||||||||||
HER2 | 59 | 85 | / | / | ||||||||||
MUC1 | 36 | 90 | / | / | ||||||||||
Li, 2018 [82] | China | Case–control | 34/32 | NA/50 | NA/69 | Serum | / | HC | SERS immunosensor | GPC1 | 59 | 58 | 0.67 | / |
34/32 | NA/50 | NA/69 | Serum | / | HC | SERS immunosensor | EGFR | 57 | 56 | 0.63 | / | |||
Jin, 2018 [49, 83] | China | Case–control | 24/46 | 61/49 | 33/50 | Serum | I-IV | HC | ELISA | ZIP4 | 92 | 80 | 0.89 | / |
24/32 | 61/44 | 33/28 | Serum | I-IV | NCd | ELISA | ZIP4 | 92 | 84 | 0.89 | / | |||
24/32 | 61/63 | 33/53 | Serum | I-IV | BD | ELISA | ZIP4 | 92 | 81 | 0.81 | / | |||
Xiao, 2019 [79] | China | Case–control | 24/26 | 59/45 | 42/85 | Plasma | / | HC | Flow cytometry | GPC1 | 72* | 84* | 0.89 | / |
CD82 | 86* | 66* | 0.85 | / | ||||||||||
24/6 | 59/73 | 42/83 | Plasma | / | CP | Flow cytometry | GPC1 | 100* | 66* | 0.85 | / | |||
CD82 | 100* | 66* | 0.90 | / | ||||||||||
Buscail, 2019 [24, 54, 66] | France | Prospective | 22/28 | 70/58 | 59/28 | Serum-CD63 | I-III | NCe | Flow cytometry | GPC1 | 50 | 90 | 0.68 | / |
MPs | ||||||||||||||
Rodrigues, 2019 [33] a | USA | Case–control | 20/12 | / | 45/25 | Serum | / | NCk | nanoparticle-and dyebased fluorescent immunoassay | EpCAM | 75* | 100* | 0.92 | |
EphA2 | 95* | 83* | 0.93 | |||||||||||
Zhou, 2020 [62] | China | Case–control | 30/10 | 60/58 | / | Plasma | I-IV | NCf | 3D mircrofluidic chip | EphA2 | 69* | 99* | 0.85 | |
Wei, 2020 [60] | China | Case–control | 204/74 | 62/NA | / | serum | I-IV | HC | Enzyme-Linked Immunosorbent Assays | EphA2 | 83 | 94 | 0.94 | |
204/75 | 62/NA | / | BPD | EphA2 | 81 | 94 | 0.92 | |||||||
94/74 | / | / | I-II | HC | EphA2 | 83 | 94 | 0.92 | ||||||
94/75 | / | / | BPD | EphA2 | 84 | 88 | 0.90 | |||||||
Fahrmann,2020 [58]a | USA | Case–control | 6/21 | / | / | Plasma | IV | HC | SOMAscan assay | ASGR1 | / | / | 0.89 | 0.0026 |
ANXA1 | / | / | 0.99 | 0.0000 | ||||||||||
IL12RB2 | / | / | 0.85 | 0.0083 | ||||||||||
ADAM9 | / | / | 0.98 | 0.0000 | ||||||||||
TGFBR2 | / | / | 0.85 | 0.0083 | ||||||||||
EDA | / | / | 0.85 | 0.0083 | ||||||||||
BMPR2 | / | / | 0.88 | 0.0034 | ||||||||||
TYRO3 | / | / | 0.87 | 0.0043 | ||||||||||
FLRT3 | / | / | 0.87 | 0.0054 | ||||||||||
SLAMF6 | / | / | 0.95 | 0.0002 | ||||||||||
CD4 | / | / | 0.87 | 0.0054 | ||||||||||
RXFP1 | / | / | 0.87 | 0.0054 | ||||||||||
Li, 2021 [76] a | China | Case–control | 21/29 | 54/62 | 43/55 | plasma | / | HC | AbMB-bioChol paltform | EGFR | 52* | 93* | 0.74 | |
EpCAM | 94* | 48* | 0.68 | |||||||||||
GPC1 | 43* | 89* | 0.72 | |||||||||||
EphA2 | 47* | 86* | 0.64 | |||||||||||
MPs | ||||||||||||||
Moutinho-R, 2021 [75] | Portugal | prospective | 60/29 | 67/54 | 55/76 | serum | I-IV | CP | flow cytometry | GPC1 | 98 | 86 | 0.96 | < 0.0001 |
15/29 | NA/54 | NA /76 | I | 100* | 96* | 0.97 | ||||||||
45/29 | NA /54 | NA /76 | II-IV | 95* | 97* | 0.96 | ||||||||
nMPs | ||||||||||||||
Yang, 2017 [47] a | USA | Prospective | 22/21 | / | / | plasma | / | NCc | NPS chip | WNT2 | 64 | 76 | / | / |
GRP94 | 55 | 71 | / | / | ||||||||||
Case–control | 22/10 | 68/48 | 36/40 | plasma | II-IV | HC | NPS chip | B7-H3 | 50 | 100 | 0.75 | / | ||
Li, 2018 [82] | China | Case–control | 71/32 | 60/50 | 54/69 | Serum | I-IV | HC | SERS immunosensor | MIF | 63 | 76 | 0.89 | / |
Lux, 2019 [54, 81] | Germany | Case–control | 55/34 | 67/NA | 53/NA | Serum | I-IV | NCg | Flow cytometry | c-Met | 70 | 85 | 0.75* | / |
Fahrmann,2020 [58]a | USA | Case–control | 6/21 | / | / | Plasma | IV | HC | SOMAscan assay | IFNGR2 | / | / | 0.87 | 0.0054 |
TPSG1 | / | / | 0.94 | 0.0003 | ||||||||||
Yang, 2021 [69] | China | Case–control | 62/42 | / | 48/ NA | plasma | I-IV | NCh | Enzyme-linked immunosorbert assay | ALIX | 53 | 84 | 0.73 | 0.0003 |
Zheng, 2022 [67] | China | Case–control | 57/84 | / | 31/39 | plasma | II-IV | HC | MALDI-TOF MS | SAA1 | 96 | 28 | 0.61 | / |
FGG | 40 | 87 | 0.62 | / | ||||||||||
nMPs | ||||||||||||||
Fahrmann,2020 [58]a | USA | Case–control | 6/21 | / | / | Plasma | IV | HC | SOMAscan assay | MAPKAPK2 | / | / | 0.94 | 0.0004 |
PDXK | / | / | 0.94 | 0.0003 | ||||||||||
PLCG1 | / | / | 0.94 | 0.0004 | ||||||||||
INSR | / | / | 0.94 | 0.0004 | ||||||||||
IL34 | / | / | 0.93 | 0.0006 | ||||||||||
AIP | / | / | 0.93 | 0.0006 | ||||||||||
YES1 | / | / | 0.93 | 0.0006 | ||||||||||
DYNLRB1 | / | / | 0.93 | 0.0006 | ||||||||||
IDE | / | / | 0.93 | 0.0006 | ||||||||||
CCL28 | / | / | 0.93 | 0.0006 | ||||||||||
nMPs | ||||||||||||||
Fahrmann,2020 [58]a | USA | Case–control | 6/21 | / | / | Plasma | IV | HC | SOMAscan assay | C5 C6 | / | / | 0.92 | 0.0008 |
CD109 | / | / | 0.92 | 0.0008 | ||||||||||
CAMK2A | / | / | 0.92 | 0.0008 | ||||||||||
TNFSF14 | / | / | 0.91 | 0.0011 | ||||||||||
MMP14 | / | / | 0.91 | 0.0011 | ||||||||||
PRKCI | / | / | 0.91 | 0.0011 | ||||||||||
MAP2K1 | / | / | 0.91 | 0.0011 | ||||||||||
KYNU | / | / | 0.91 | 0.0011 | ||||||||||
KIF23 | / | / | 0.91 | 0.0011 | ||||||||||
IL27RA | / | / | 0.91 | 0.0011 | ||||||||||
IMPDH1 | / | / | 0.91 | 0.0011 | ||||||||||
TNFRSF13B | / | / | 0.91 | 0.0011 | ||||||||||
SEMA6B | / | / | 0.91 | 0.0011 | ||||||||||
AIMP1 | / | / | 0.91 | 0.0011 | ||||||||||
NMT1 | / | / | 0.90 | 0.0015 | ||||||||||
EPHA5 | / | / | 0.90 | 0.0015 | ||||||||||
MSLN | / | / | 0.90 | 0.0015 | ||||||||||
IBSP | / | / | 0.90 | 0.0015 | ||||||||||
TNFSF13B | / | / | 0.90 | 0.0015 | ||||||||||
CTF1 | / | / | 0.90 | 0.0015 | ||||||||||
BCL2L1 | / | / | 0.90 | 0.0015 | ||||||||||
IL1A | / | / | 0.90 | 0.0015 | ||||||||||
MAPK12 | / | / | 0.90 | 0.0015 | ||||||||||
FABP1 | / | / | 0.90 | 0.0020 | ||||||||||
CCL17 | / | / | 0.90 | 0.0020 | ||||||||||
nMPs | ||||||||||||||
Fahrmann,2020 [58]a | USA | Case–control | 6/21 | / | / | Plasma | IV | HC | SOMAscan assay | SPARCL1 | / | / | 0.90 | 0.0020 |
LCK | / | / | 0.90 | 0.0020 | ||||||||||
CCL3L1 | / | / | 0.90 | 0.0020 | ||||||||||
PDE9A | / | / | 0.90 | 0.0020 | ||||||||||
PRDX5 | / | / | 0.90 | 0.0020 | ||||||||||
CD300C | / | / | 0.90 | 0.0020 | ||||||||||
BCL2L2 | / | / | 0.90 | 0.0020 | ||||||||||
CSRP3 | / | / | 0.90 | 0.0020 | ||||||||||
GDF2 | / | / | 0.90 | 0.0020 | ||||||||||
IL17RB | / | / | 0.90 | 0.0020 | ||||||||||
LGALS3BP | / | / | 0.90 | 0.0020 | ||||||||||
SEMA6A | / | / | 0.90 | 0.0020 | ||||||||||
CLEC11A | / | / | 0.90 | 0.0020 | ||||||||||
UBC | / | / | 0.89 | 0.0026 | ||||||||||
HIPK3 | / | / | 0.89 | 0.0026 | ||||||||||
PARK7 | / | / | 0.89 | 0.0026 | ||||||||||
MMP13 | / | / | 0.89 | 0.0026 | ||||||||||
FGFR4 | / | / | 0.89 | 0.0026 | ||||||||||
FGF5 | / | / | 0.89 | 0.0026 | ||||||||||
DDR1 | / | / | 0.89 | 0.0026 | ||||||||||
PDK1 | / | / | 0.89 | 0.0026 | ||||||||||
CXCL8 | / | / | 0.89 | 0.0026 | ||||||||||
GDF11 | / | / | 0.89 | 0.0026 | ||||||||||
IDUA | / | / | 0.89 | 0.0026 | ||||||||||
CA3 | / | / | 0.89 | 0.0026 | ||||||||||
nMPs | ||||||||||||||
Fahrmann,2020 [58]a | USA | Case–control | 6/21 | / | / | Plasma | IV | HC | SOMAscan assay | DYNLL1 | / | / | 0.89 | 0.0026 |
ACVRL1 | / | / | 0.89 | 0.0026 | ||||||||||
CXCL1 | / | / | 0.88 | 0.0034 | ||||||||||
CRLF1/CLCF1 | / | / | 0.88 | 0.0034 | ||||||||||
DHH | / | / | 0.88 | 0.0034 | ||||||||||
ENTPD5 | / | / | 0.88 | 0.0034 | ||||||||||
UBE2G2 | / | / | 0.88 | 0.0034 | ||||||||||
IFNG | / | / | 0.88 | 0.0034 | ||||||||||
CHEK2 | / | / | 0.88 | 0.0034 | ||||||||||
LTA LTB | / | / | 0.87 | 0.0043 | ||||||||||
FAM107A | / | / | 0.87 | 0.0043 | ||||||||||
TNFRSF18 | / | / | 0.87 | 0.0043 | ||||||||||
KLK6 | / | / | 0.87 | 0.0043 | ||||||||||
PPP3R1 | / | / | 0.87 | 0.0043 | ||||||||||
CD244 | / | / | 1.00 | 0.0000 | ||||||||||
ETHE1 | / | / | 0.87 | 0.0043 | ||||||||||
PDXP | / | / | 0.87 | 0.0043 | ||||||||||
IFNB1 | / | / | 0.87 | 0.0043 | ||||||||||
IL36A | / | / | 0.87 | 0.0043 | ||||||||||
KLK14 | / | / | 0.87 | 0.0043 | ||||||||||
IL1RN | / | / | 0.87 | 0.0043 | ||||||||||
F3 | / | / | 0.87 | 0.0043 | ||||||||||
MAPK11 | / | / | 0.87 | 0.0054 | ||||||||||
TNFRSF14 | / | / | 0.87 | 0.0054 | ||||||||||
PRLR | / | / | 0.87 | 0.0054 | ||||||||||
nMPs | ||||||||||||||
Fahrmann,2020 [58]a | USA | Case–control | 6/21 | / | / | Plasma | IV | HC | SOMAscan assay | VEGFA | / | / | 0.87 | 0.0054 |
FABP5 | / | / | 0.87 | 0.0054 | ||||||||||
CDH3 | / | / | 0.87 | 0.0054 | ||||||||||
ISG15 | / | / | 0.87 | 0.0054 | ||||||||||
CKM | / | / | 0.87 | 0.0054 | ||||||||||
ABL2 | / | / | 0.87 | 0.0054 | ||||||||||
TNFSF11 | / | / | 0.86 | 0.0067 | ||||||||||
CA10 | / | / | 0.86 | 0.0067 | ||||||||||
EPHA2 | / | / | 0.86 | 0.0067 | ||||||||||
HK2 | / | / | 0.86 | 0.0067 | ||||||||||
STK16 | / | / | 0.86 | 0.0067 | ||||||||||
CD47 | / | / | 0.86 | 0.0067 | ||||||||||
PAK7 | / | / | 0.86 | 0.0067 | ||||||||||
CDK2 CCNA2 | / | / | 0.86 | 0.0067 | ||||||||||
ZAP70 | / | / | 0.86 | 0.0067 | ||||||||||
CXCL5 | / | / | 0.86 | 0.0067 | ||||||||||
MAPK8 | / | / | 0.86 | 0.0067 | ||||||||||
IL17F | / | / | 0.86 | 0.0067 | ||||||||||
PDGFRA | / | / | 0.86 | 0.0067 | ||||||||||
FGF2 | / | / | 0.86 | 0.0067 | ||||||||||
AFP | / | / | 0.86 | 0.0067 | ||||||||||
PECAM1 | / | / | 0.86 | 0.0067 | ||||||||||
STAT6 | / | / | 0.85 | 0.0083 | ||||||||||
TOP1 | / | / | 0.85 | 0.0083 | ||||||||||
CRLF2 | / | / | 0.85 | 0.0083 | ||||||||||
nMPs | ||||||||||||||
Fahrmann,2020 [58]a | USA | Case–control | 6/21 | / | / | Plasma | IV | HC | SOMAscan assay | TLR4 | / | / | 0.85 | 0.0083 |
BCL2 | / | / | 0.85 | 0.0083 | ||||||||||
TNF | / | / | 0.85 | 0.0083 | ||||||||||
C1QBP | / | / | 0.85 | 0.0083 | ||||||||||
CLEC11A | / | / | 0.85 | 0.0083 | ||||||||||
GDF9 | / | / | 0.85 | 0.0083 | ||||||||||
ING1 | / | / | 0.85 | 0.0083 | ||||||||||
BIRC5 | / | / | 0.85 | 0.0083 | ||||||||||
B2M | / | / | 0.85 | 0.0083 | ||||||||||
ERP29 | / | / | 0.85 | 0.0083 | ||||||||||
FLT3LG | / | / | 0.85 | 0.0083 | ||||||||||
NAPA | / | / | 0.85 | 0.0083 | ||||||||||
GCKR | / | / | 0.85 | 0.0083 | ||||||||||
EPHA1 | / | / | 0.85 | 0.0083 | ||||||||||
HSD17B10 | / | / | 0.85 | 0.0083 | ||||||||||
CEBPB | / | / | 0.85 | 0.0083 | ||||||||||
SSRP1 | / | / | 0.85 | 0.0083 | ||||||||||
SPHK2 | / | / | 0.85 | 0.0083 | ||||||||||
CCL22 | / | / | 0.85 | 0.0083 | ||||||||||
GDF5 | / | / | 0.85 | 0.0083 | ||||||||||
APOD | / | / | 0.85 | 0.0083 | ||||||||||
POR | / | / | 0.99 | 0.0000 | ||||||||||
LY9 | / | / | 0.97 | 0.0001 | ||||||||||
IFNGR1 | / | / | 0.96 | 0.0001 | ||||||||||
GSK3A/B | / | / | 0.96 | 0.0001 | ||||||||||
nMPs | ||||||||||||||
Fahrmann,2020 [58]a | USA | Case–control | 6/21 | / | / | Plasma | IV | HC | SOMAscan assay | FLT3 | / | / | 0.95 | 0.0002 |
CSNK2A1 | / | / | 0.95 | 0.0002 | ||||||||||
PIK3CA/R1 | / | / | 0.95 | 0.0002 | ||||||||||
LIN7B | / | / | 0.95 | 0.0002 | ||||||||||
METAP1 | / | / | 0.95 | 0.0002 | ||||||||||
MAPK13 | / | / | 0.90 | 0.0015 | ||||||||||
FAS | / | / | 0.94 | 0.0003 |
SENs, SPEs and AUCs in bold fonts represent results from validation set (non-bold fonts represent results without validation)
AUC area under the curve, BD Biliary disease, BPD benign pancreatic disease, CP chronic pancreatitis, HC healthy control, IPMN intraductal papillary mucinous neoplasm, NC noncancerous, nPES nanoplasmon-enhanced scattering, NPS nanoplasmonic sensor, SERS surface-Enhanced Raman Scattering, SOMAscan assay slow off-rate modified DNA aptamer, nMPs nonMembrane proteints, MPs Membrane proteins, SEN sensitivity, SPE specificity, MALDI-TOF MS matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, AbMB antibody-conjugated magnetic beads
arepresent markers extracted from extracellular vesicles
bBPD and HC
cbenign pancreatic tumor, CP, and HC
dbenign pancreatic tumor and pancreatitis
eHC, CP, and IPMN
fno history of cancer
gserous cyst adenoma and CP
hwell-differentiated pancratic neuroendocrine tumor, pancreatic cystic lesions, choronic pancreatitis, and HC
kliver injury, pancreatitis, and cholangitis
*represent estimated value
p value indicates the p value of AUC