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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.
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