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Table 2. Clinical utilities of CTCs in gastric cancer
Molucular
Author Year Case Method Clinical utility
marker
Wu et al. [53] 2006 64 MAH TERT, CK19, The expression of all 4 mRNA markers was
CEA, MUC an independent predictor for postoperative
recurrence/metastasis
Uen et al. [54] 2006 52 RT-PCR MUC1, c-Met OS was shoter in patients with positive c-Met
or MUC1 mRNA expression than in patients
with negative c-Met or MUC1
Pituch-Noworolska et al. [55] 2007 57 ICC CK8, 19, 20 There was no significant difference in the
5-year survival of patients, with or without CK
in the blood
Koga et al. [56] 2008 101 RT-PCR CK18, 19, 20 CK19 was a better marker than CK18 and
CK20, and could be clinically useful to
estimate prognosis
Yie et al. [57] 2008 55 RT-PCR, ELISA Survivin Survivin-expressing CTCs were statistically
shown to be a significant and independent
predictor for cancer recurrence
Mimori et al. [58] 2008 810 RT-PCR CK7, 19, 20, Elevated expression of VEGFR-1 was
VEGFR associated with hematogenous metastases in
gastric cancer
Bertazza et al. [59] 2009 70 RT-PCR Survivin Survivin mRNA levels were retained as an
independent prognostic factor
Qiu et al. [60] 2010 123 RT-PCR CEA CEA mRNA positivity were independent
factors for DFS
Arigami et al. [61] 2010 94 RT-PCR B7-H3 The 5-year OS rate was significantly lower in
patients with than without B7-H4 expression
Matsusaka et al. [62] 2010 52 CellSearch EpCAM, CK8, Patients with ≥ 4 CTCs at 2-week points and
18, 19 4-week points after initiation of chemotherapy
had a shorter median PFS
Cao et al. [63] 2011 98 RT-PCR, ELISA Survivin The detection of CTCs expressing survivin
mRNA was an independent prognostic factors
of DFS
Ito et al. [64] 2012 65 ICC GFP, EpCAM There was a significant relationship between
the number of GFP-positive CTCs and overall
survival
Arigami et al. [65] 2013 93 RT-PCR STC2 The 5-year OS rate was significantly lower in
patients with STC2 expressioncompared to
patients without STC2 expression
Uenosono et al. [66] 2013 148 CellSearch EpCAM, CK8, The detection of CTCs was an indepentdent
18, 19 factor of shorter OS and PFS
Okabe et al. [67] 2015 136 CellSearch EpCAM, CK8, The detection of CTCs was an indepentdent
18, 19 factor of shorter PFS
Lee et al. [68] 2015 100 CellSearch EpCAM, CK8, The detection of CTCs was associated with
18, 19 poor response to chemotherapy in metastatic
gastric cancer
Kubisch et al. [69] 2015 62 Immune- MUC1, EpCAM The detection of CTCs was associated with
magnetic shorter PFS and OS for patients undergoing
chemotherapy
Li et al. [70] 2016 136 CellSearch EpCAM, CK8, Conversion to a favourable CTC level (< 3
18, 19 CTCs per 7.5 mL) following therapy improved
the prognosis
MAH: membrane-array hybridization; ICC: immunocytochemistry; ELISA: enzyme-linked immunosorbent assay; DFS: disease free
survival; OS: overall survival; PFS: progression free survival; CTC: circulating tumor cell; EpCAM: epithelial cells adhesion molecule; RT-
PCR: reverse transcription polymerase chain reaction
serve as a biomarker of therapy option.
Furthermore, the advances in single-cell technologies have enabled individual CTC characterization, leading
[48]
to improved understanding about tumor heterogeneity. Alix-Panabières and Pantel reviewed genomic,
transcriptomic, and proteomic characterization of single CTCs in different cancer types, and suggested that
analysis of single CTCs may play a key role in understanding the mechanism of resistance to cancer therapy.