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Table 3 Clinical Application value of CTCs in CRC

From: Detection and clinical significance of circulating tumor cells in colorectal cancer

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]