Table 2.

sEV protein biomarkers for PDAC diagnosis/prognosis

Biomarkers	Sources	Patient numbers	Discoveries and diagnostic performance	Ref.
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]
KRASmut, P53mut	Plasma	Stage I n = 16	Mutant proteins KRASmut and/or P53mut 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]