Table 2 sEV protein biomarkers for PDAC diagnosis/prognosis

GPC-1

Plasma

N = 27

High GPC-1 in sEVs may be able to determine PDAC tumor size and disease burden. AUC of 0.59 was achieved for PDAC detection.

[99]

MIF

Plasma

N = 40

MIF was highly expressed in sEVs from PDAC patients (PDAC patients without liver metastasis vs. healthy controls P < 0.01)

[83]

EpCAM

Plasma

N = 19

PDAC patients had a high level of EpCAM in sEVs, and the level changed during palliative chemotherapy treatment

[100]

EphA2

Plasma

N = 49

EphA2 in sEVs could distinguish pancreatic cancer patients from pancreatitis patients and healthy subjects with AUC of 0.93–0.96

[101]

KRAS^mut, P53^mut

Plasma

Stage I n = 16

Mutant proteins KRAS^mut and/or P53^mut were detected in 15 of the 16 early stage PDAC patients

[102]

EGFR, CA19-9

Plasma

N = 5

More abundant of EGFR (5 fold) and CA19-9 (15 fold) enriched sEVs in PDAC patients than healthy donors

[103]

EGFR, EpCAM, MUC1, GPC1, WNT2

Plasma

N = 22

The five-marker signature yielded a more accurate diagnosis of PDAC than CA19-9 and a single sEV biomarker with sensitivity of 86% (CI, 65 to 97%) and a specificity of 81% (CI, 58 to 95%) in prospective cohort

[95]

GPC-1, CD63

Plasma, serum

N = 20

Twenty PDAC patient samples could be distinguished from 11 healthy subjects with 99% sensitivity and 82% specificity

[104]

GPC-1, EpCAM, CD44V6

Plasma

N = 9

The PDAC EV signature of the three protein biomarkers could be used for PDAC diagnosis with AUC of 1.000 (95% CI: 84.6–100%) and showed strong correlation with cancer stages

[105]

GPC-1

Serum

N = 190

GPC-1 in sEVs showed higher level in PDAC patients than healthy donors with P < 0.0001

[96, 106, 107]

c-Met

Serum

N = 55

Diagnostic test based on c-Met in sEVs resulted in a sensitivity of 70%, a specificity of 85%

[108]

CKAP4

Serum

N = 47

The CKAP4 levels in sEVs were higher in patients with PDAC than healthy control individuals

[109]

ANXA6

Serum

N = 108

ANXA6 level in sEVs could be used to diagnose PDAC patients with AUC of 0.979 and improved sensitivity and specificity

[110]

ZIP4

Serum

N = 24

The level of ZIP4 in sEVs showed promising diagnostic efficacy between PDAC and control group with AUC of 0.893

[97]

ADAM8

Serum

N = 5

ADAM8 in EVs from PDAC patients or precursor lesions had significantly higher expression when compared to healthy individuals with P < 0.0001or P = 0.0139, respectively

[64]

CD41, CD61, CD63

Serum

N = 39

The levels of CD41, CD61 and CD63 in sEVs increased in PDAC patients then healthy donors with AUC of 0.678, 0.652 and 0.846, respectively

[111]

CD44v6, C1QBP

Serum

N = 142

Highly expressed CD44v6 and C1QBP in sEVs were promising biomarkers for predicting prognosis and liver metastasis in patients with PDAC

[112]

LRG-1, GPC-1

Serum

N = 15

Combination of LRG-1 and GPC-1 positive sEVs could improve the diagnostic accuracy of PDAC with AUC of 0.95, even for the early stage PDAC.

[113]

Integrin α6

Blood

N/A

The expression of Integrin α6 in sEVs from blood of PDAC patients significantly decreased after surgery and increased several months before clinical recurrence

[114]

Mucin-4, Mucin-5AC, Mucin-6, Mucin-16, etc.

Pancreatic duct fluid

N = 4

Unique proteins were detected exclusively in sEVs from Pancreatic duct fluid by mass spectroscopy (MS)

[115]

Combination of 35 proteins

Pancreatic duct fluid

N = 13

Pancreatic duct fluid proteins were potential biomarkers of patients with different pancreatic diagnoses

[116]