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Wang et al. Hepatoma Res 2020;6:61 I http://dx.doi.org/10.20517/2394-5079.2020.55 Page 7 of 15

Table 2. Applications of CTC detection in HCC
Quality of
Techniques/
Year Model Objective Main findings the evidence Ref.
Platform
(GRADE)
2011 Flow 82 HCC patients Prognostic significance of Circulating cancer stem cells > 0.01% ●●○○ [86]
cytometric stem cell-like CTCs in HCC predicted post-hepatectomy HCC Low
analysis undergoing liver resection recurrence with high accuracy
2012 In vivo flow HCC orthotopic Monitor CTC dynamics in The number of CTCs and early ●○○○ [99]
cytometry metastatic tumor vivo metastases rates decreased significantly Very Low
model (mouse) after the resection of primary tumor
2013 CellSearch 123 HCC patients Prognostic significance of A preoperative EpCAM CTCs ≥ 2/7.5 ●●●○ [17]
CTCs in HCC undergoing mL of blood was an independent Moderate
liver resection prognostic factor for tumor recurrence;
such prognostic value retained in patient
subgroups; a significant decrease of
CTC-positive rates and numbers was
observed 1 month after resection
2013 CellSearch 59 HCC patients Prognostic significance of Presence of EpCAM-positive CTC ●●○○ [77]
CTCs in HCC undergoing was associated with intermediate or Low
liver resection advanced HCC stage and worse OS
2013 Flow 60 HCC patients Prognostic significance of Increased numbers of ICAM-1(+) cells ●●○○ [46]
cytometric stem cell-like CTCs in HCC in blood samples of HCC patients Low
analysis undergoing liver resection correlated with worse clinical outcomes
2013 ASGPR 60 HCC patients Relationship between Twist and Vimentin expression levels ●●○○ [87]
sorting the EMT status of CTCs in CTCs could serve as promising Low
and HCC metastasis and biomarkers for evaluating metastasis
prognosis after surgical and prognosis in HCC
resection
2014 qRT-PCR- 299 HCC patients Diagnostic value of CTC; Negative enrichment and qRT-PCR- ●●●○ [71]
based Clinical significance of based platform can effectively detect Moderate
platform CTCs in patients treated CTCs; the platform might be clinically
with surgical resection, useful in auxiliary diagnosis, treatment
TACE and radiotherapy response assessment, and early decision
making of antitumor strategies for HCC
2015 CellSearch 20 HCC patients Prognostic significance of CTC detection was associated with ●○○○ [78]
CTCs and CTC-based DNA elevated AFP, vascular invasion, and Very Low
signature poor prognostic factors; sequencing
of CTC DNA identified known HCC
mutations
2015 In vivo flow HCC orthotopic Monitor CTC dynamics CTCs can be a biomarker in predicting ●○○○ [107]
cytometry metastatic tumor following sorafenib disease progression and monitoring Very Low
model (mouse) treatment in vivo therapeutic efficacy in HCC
2016 qRT-PCR- 49 HCC patients Prognostic significance Combination of EpCAM CTC and T ●○○○ [83]
based of CTCs and T regulatory regulatory/CD4(+) cell may be a novel Very Low
platform cell in the prediction of prognostic predictor for HCC patients
postoperative recurrence
2016 CanPatrol 33 HCC patients Diagnostic value of CTCs of Epithelial-mesenchymal-mixed CTCs ●○○○ [73]
platform EMT phenotypes in HCC; might be a vital factor for intrahepatic Very Low
relationship between the metastasis, and mesenchymal CTCs
EMT process of CTCs and predicated extrahepatic metastasis in
HCC HCC
2016 qRT-PCR- 72 HCC patients Dynamic monitoring of Increased AFP mRNA(+) CTCs can be a ●●○○ [101]
based CTC counts after surgical predictor for HCC metastasis before and Low
platform resection after hepatectomy
2016 Density 59 HCC patients Determining pERK and pERK+/pAkt- CTCs were the ●●○○ [109]
gradient pAkt expressions in CTCs most sensitive to sorafenib and an Low
centrifugation isolated from HCC patients independent predictive factor of PFS in
HCC patients treated with sorafenib
2016 Microfluidic 36 HCC patients Isolation of viable CTCs of The device can accurately enumerate ●○○○ [110]
device and HCC for their culture and CTCs and release viable CTCs for in Very Low
ASGPR drug sensitivity assays vitro culture and further functional
sorting assays
2017 CellSearch 61 HCC patients Prognostic significance of Detection of CTC prior to curative- ●●○○ [80]
CTCs in HCC undergoing intended liver resection disclosed an Low
liver resection elevated risk of HCC recurrence
2017 CanPatrol 195 HCC patients EMT phenotypes of CTCs in CTCs count and EMT classification ●●○○ [88]
platform the early diagnosis of HCC are correlated with clinical stages and Low
metastasis and progression metastasis of HCC
after surgical resection