Table 1.

Liquid biopsy in the early diagnosis of pancreatic cancer

Ref.	Journal	No. of patients	Biomarker	Method	Main findings
Ankeny et al[76], 2016	Br J Cancer	72	CTC	Microfluidic NanoVelcro CTC chip	Detection rate of PDAC: 54/72 (sensitivity = 75.0%, specificity = 96.4%)
Rhim et al[77], 2014	Gastroenterology	51	CTC	Microfluidic geometrically enhanced differential immunocapture	CTC (≥ 3) in 33% of patients with cystic lesions and no clinical diagnosis of cancer, 73% with PDAC, and 0% of controls
Xu et al[78], 2017	Int J Mol Sci	40	CTC	NE-iFISH	The positive rate of diagnosis of PDAC is nearly 97% in combination with CA19-9
Poruk et al[79], 2017	Clin Cancer Res	60	CTC	ISET method & immunofluorescence	The positive rate is 12% in stageⅠPDAC
Gao et al[80], 2016	J Exp Clin Cancer Res	25	CTC	SE-iFISH platform	Sensitivity of 88 % and specificity of 90 % in PDAC
Kulemann et al[81], 2015	Pancreas	11	CTC	ScreenCell; Cyto kit	No difference in the rate of CTC detection between early-stage and advanced-stage diseases (P = 0.71)
Melo et al[33], 2015	Nature	56	Exosome	FACS analysis	The sensitivity and specificity of GPC1+ circulating exosomes in diagnosing PDAC were both 100%
Buscail et al[82], 2019	Cancers	30	Exosome and CTC	FACS, Cellsearch and RosetteSepTM	Combining quantification of GPC1-positive exosomes and CTC detection identified all the PDAC patients, showed a negative predictive value of 100%, and an overall diagnostic accuracy of 91%
Lai et al[83], 2017	Cancer Lett	40	Exosome and miRNA	LC-MS & RT-qPCR	High levels of exosomal miR-10b, miR-21, miR-30c, and miR-181a and low levels of miR-let7a differentiated PDAC from healthy and chronic pancreatitis samples
Liang et al[84], 2017	Nat Biomed Eng	23	EV	nPES assay	Pre-therapy EphA2-EV blood levels accurately distinguished stage I/II pancreatic cancer patients from NC (AUC = 0.96) and pancreatitis patients (AUC = 0.93)
Que et al[85], 2013	World J Surg Oncol	49	miRNA	RT-PCR	Serum exosomal miR-17-5p was higher in PDAC patients than in non–PDAC patients and healthy participants
Cote et al[86], 2014	Am J Gastroenterol	215	miRNA	RT-PCR	Increased expression of miRNA-10b, -155, and -106b in plasma appears highly accurate in diagnosing PDAC
Ouyang et al[87], 2015	Oncogene	42	miRNA	RT-PCR	Plasma miR-10b levels significantly increased in comparison with normal controls
Slater et al[88], 2014	Transl Oncol	59	miRNA	Real-time PCR	A combination test of miRNA-196a and miRNA-196b, whose expression is upregulated from the PanIN state, can identify patients with PanIN 2/3
Madhavan et al[89], 2015	Int J Cancer	220	Exosome and miRNA	miRNeasyMinikit, RT-PCR, qRT-PCR and flow cytometry	The selected miR-1246, miR-4644, miR-3976 and miR-4306 were significantly upregulated in 83% of PDAC serum-exosomes, but rarely in control groups

AUC: Area under the curve; CA19-9: Carbohydrate antigen 19-9; CTC: Circulating tumor cell; EphA2: Ephrin type-A receptor 2; EV: Extracellular vesicles; FACS: Fluorescence-activated cell sorting; ISET: Isolation by size of epithelial tumor cells; LC-MS: Liquid chromatography-tandemmass spectrometry; miRNA: microRNA; nPES: Nanoplasmon-enhanced scattering; NC: Normal healthy control; NE-iFISH: Negative enrichment immunofluorescence and in situ hybridization of chromosome 8; PDAC: Pancreatic ductal adenocarcinoma; RT-qPCR: Quantitative reverse transcription polymerase chain reaction; SE-iFISH: Subtraction enrichment and immunostaining-fluorescence in situ hybridization.