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. 2022 May 23;22:573. doi: 10.1186/s12885-022-09463-x

Table 2.

Diagnostic performance of proteins in extracellular vesicles for pancreatic cancer

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