Table 3.

Clinical Application value of CTCs in CRC

Patient number	Technique	Marker	CTC cut-off	Patient ratio (%)	Significance	Ref
10	ClearCell FX LSC-MS	–	–	–	Differences in the metabolic profile can be used to discriminate CTCs andlymphocytes obtained from the same patient and CTCs of different cancer types.	[93]
50	RT-PCR	–	–	82.00	The CTCs number obtained by quantifying mRNAs of six CRC-related genes (CEA,EpCAM, CK19, MUC1, EGFR and C-Met) in the blood was associated with 2-year PFS.	[94]
132	CellSearch	EpCAM	≥3CTC/7.5 ml	19.00	Baseline and 4 weeks CTCs counts ≥3/7.5 mL in CRC patients with potentiallyresectable liver metastases were associated with decreased OS.	[95]
44	CellSearch	EpCAM	≥2CTC/7.5 ml	18.6	Preoperative CTCs counts ≥2/7.5 mL in CRC patients with resected liver metastaseswere associated with decreased DFS and OS.	[97]
130	MACS	CD45	≥2CTC/3.2 ml	51.54	Postoperative CTCs counts ≥2/3.2 mL in non-mCRC was associated with decreased RFS.	[99]
66	CanPatrol Multiplex mRNA-ISH	–	≥6CTC/5 ml	86.4	CTCs counts ≥6/5 ml was associated with decreased PFS and OS. LGR5 expressionin CTCs may serve as a marker for CRC metastasis.	[100]
78	MACS qRT-PCR	EpCAM CD45	–	–	Akt-2 (≥0.25 ng μl-1) expression in CTCs was associated decreased median PFS.	[103]
91	CanPatrol mRNA-ISH	–	≥3CTC/5 ml ≥1mCTC/5 ml	CTC 56.0 mCTC 50.5	Mesenchymal CTC counts ≥1/5 ml and COX-2 expression in mCTCs were associatedwith distance metastasis.	[104]
42	CellSearch	EpCAM	≥3CTC/7.5 ml	52.3	Patients with CTC ≥3/7.5 ml may benefit from the intensive 4-drug regimen (irinotecan,oxaliplatin, and tegafur-uracil with leucovorin and cetuximab).	[106]
55	MACS Flow Cytometry	EpCAM CD45	> 30CTC/ml	52.7	CTCs counts > 30/ml in mCRC patients treated with chemotherapy was associatedwith decreased PFS and OS.	[107]
138	ISET device-CTCBIOPSY	–	≥1CTC/2.5 ml	45.7	Post curative resection CTCs counts > 1/2.5 ml was associated shorter 3-year RFS rate.	[108]
589	CellSearch	EpCAM	≥3CTC/7.5 ml	41	Baseline CTCs counts ≥3/7.5 mL was associated with clinical or pathologic featuresassociated with poor Prognosis.	[110]
628	qRT-PCR	–	–	33.6	Plastin3 is a CTC marker specifically expressed in metastatic colorectal cancer cells.Preoperative PLS3-positive CTCs in peripheral blood were associated decreased DFSand OS.	[112]
14	ISET qPCR	–	–	60	The CTCs captured by the ISET system allows for counting, genotypic and phenotypiccharacterization. Using a qPCR method, KRAS exon 2 mutations were successfullydetected in CTCs of patients with RAS-WT mCRC who treated with first-linechemotherapy and monoclonal antibodies.	[116]
61	CellSearch ASONE Cell PickingSystem PCR/WGA	EpCAM	≥1CTC/7.5 ml	44.3	CTC heterozygosity and heterogeneity exist in KRAS status among CTCs within apatient and between CTCs and tumor tissues.	[117]
50	CellSearch Multiplex-PCR	EpCAM	≥3CTC/7.5 ml	46	CTCs counts ≥3/7.5 mL at baseline and day 21 after initiation of regorafenib wereassociated decreased PFS and OS. Patients had significantly increased EGFR expressionat day 21 and/or PD compared to baseline.	[118]
94	MACS RT-qPCR	EpCAM	–	–	Patients with higher gene panel expression (composed of GAPDH, VIL1, CLU, TIMP1,TLN1, LOXL3 and ZEB2) at baseline or increased gene panel expression duringtreatment had decreased PFS and OS. This CTC detection panel had increasedreliability compared to computed tomography scan.	[132]
106	MACS qRT-PCR	CD45 Pan-CK	≥5CTC/ml	100	HAI/target therapy with drugs selected by liquid biopsy precision oncotherapy isa safe and efficacious alternative therapeutic strategy for unresectable colorectalliver metastases patients.	[133]