Circulating tumor cells as potential prognostic biomarkers for early-stage pancreatic cancer: A systematic review and meta-analysis

Table 1 Characteristics of the included studies

Ref.	Year	Country	Sample	Separation Solution	Markers and expression level on PC CTC	Cases	No-positive	Treatment	Outcome	Follow-up time
Xing et al[14]	2021	China	Peripheral blood	SE-iFISH	CD44+ CTEC: DAPI +/CD45-/CD31 +/CD44 +/Vimentin (+ or -) with aneuploid CEP8	73	Not reported	Surgery	OS/DFS	Median 10.8 mo (1.2-31.8 mo)
Semaan et al[15]	2021	United States	Peripheral blood	DEP-FFF	pEMT-CTC: CD45 -, EpCAM + and/or Pan-CK +, Vimentin +, DAPI +	31 early stages (74 total)	28	Surgery/neoadjuvant treatment	OS/PFS	Median 15.4 mo (0-43.1 mo)
Padillo-Ruiz et al[21]	2021	Spain	Central venous catheter and portalblood	ICC	DAPI +/CK +/CD45 -	35	35	Surgery/chemotherapy	OS/DFS	24 mo
Court et al[16]	2018	United States	Peripheral blood	NanoVelcro chip	DAPI +/CD45 -/CK +; CD45 positivity greater than 2 × background	40 early stages (126 total)	27	Surgery/chemotherapy	OS/RFS	≥ 24 mo
Cheng et al[17]	2022	China	Peripheral blood	LT-PCR	FR + CTC	25 early stages (44 total)	13	Surgery/chemotherapy	OS/DFS	Median 20 mo (6-28 mo)
White et al[18]	2021	United States	Peripheral blood and portal venous blood	CellSearch	DAPI +/CK + /CD45 -	33 early stages (34 total)	21	Surgery/neoadjuvant treatment	OS/RFS	Median 14.1 mo (0.86-1.97 mo)
Bissolati et al[19]	2014	Italy	Peripheral blood and portal venous blood	CellSearch	DAPI +/CK +/CD45 -	20	9	Surgery/chemotherapy	OS/PFS	Median 39.2 mo (36-45 mo)
Hugenschmidt et al[20]	2021	Norway	Peripheral blood	CellSearch	EpCAM +/DAPI +/CK +/CD45 -	98	7	Surgery	CSS/DFS	Median 96 mo (63-126 mo)

DEP-FFF: Dielectrophoresis-field flow fractionation; ICC: Immunocytochemistry; SE-iFISH: Subtraction enrichment and immunostaining-fluorescence in situ hybridization; PC: Pancreatic cacner ; CTCs: Circulating tumor cells; LT-PCR: Ligand-targeted polymerase chain reaction; CK: Cytokeratin; DAPI: 4',6-diamidino-2-phenylindole; EpCAM: Epithelial cell adhesion molecule; CSS: Cancer specific survival; DFS: Disease-free survival; OS: Overall survival; PFS: Progression-free survival; pEMT: Partial epithelial-mesenchymal transition.

Table 2 Quality assessment of the included studies according to the Newcastle-Ottawa Scale criteria for non-randomized studies

Ref.	Selection				Comparability			Outcome		Total stars
	Representativeness	Selection of non-exposed	Ascertainment of exposure	Outcome not present at start	Comparability on most important factors	Comparability on other risk factors	Assessment of outcome	Long enough follow-up (median ≧ 24 mo)	Completeness of follow-up
Xing et al[14]	-	1	1	1	1	-	1	-	1	6
Semaan et al[15]	-	1	1	1	1	-	1	-	1	6
Padillo-Ruiz et al[21]	-	1	1	1	1	-	1	1	1	7
Court et al[16]	-	1	1	1	1	-	1	1	1	7
Cheng et al[17]	1	1	1	1	1	-	1	-	1	7
White et al[18]	-	1	1	1	1	-	1	-	1	6
Bissolati et al[19]	1	1	1	1	1	-	1	1	1	8
Hugenschmidt et al[20]	-	1	1	1	1	-	1	1	1	7

¹Meets the criteria of the scale. A maximum of one ‘star’ for each item within the ‘Selection’ and ‘Outcome’ categories; maximum of two ‘stars’ for ‘Comparability’; -Does not meet the criteria of the scale.