Copyright
©2014 Baishideng Publishing Group Co.
World J Gastroenterol. Mar 28, 2014; 20(12): 3265-3286
Published online Mar 28, 2014. doi: 10.3748/wjg.v20.i12.3265
Published online Mar 28, 2014. doi: 10.3748/wjg.v20.i12.3265
Table 1 Detection of circulating tumor cells in gastric cancer
Characteristic and number of patients | Control (n) | Detection method | Detection rate/statistic value | Ref. | |||
Pre or post treatment | 9 (PB) | 4 | RT-PCR | CEA mRNA | 22.2% | (Pt.) | Funaki et al[133] |
0% | (Ctrl.) | ||||||
I-IV | 20 (PB) | 22 | RT-PCR | CEA mRNA | 35% | (Pt.) | Mori et al[134] |
0% | (Ctrl.) | ||||||
I-IV | 49 (PB) | 50 | RT-PCR | CK19 mRNA | 0% | (PB) | Aihara et al[135] |
21 (PV) | 0% | (PV) | |||||
0% | (Ctrl.) | ||||||
I-IV | 30 (PB) | 58 | RT-PCR | CK20 mRNA | 16.7% | (Pt.) | Soeth et al[136] |
3.4% | (Ctrl.) | ||||||
Inoperable/metastatic | 34 (PB) | 33 | RT-PCR | CK19 mRNA | 20.6% | (Pt.) | Yeh et al[137] |
0% | (Ctrl.) | ||||||
I, III, IV | 35 (PB) | 9 | RT-PCR | CEA mRNA | 45.7% | (Pt.) | Noh et al[138] |
0% | (Ctrl.) | ||||||
I-IV | 52 (PB) | 14 | RT-PCR | CK19 mRNA | 9.6% | (Pt.) | Majima et al[139] |
0% | (Ctrl.) | ||||||
CK20 mRNA | 9.6% | (Pt.) | |||||
1% | (Ctrl.) | ||||||
I-IV | 41 (PB) | RT-PCR | CEA mRNA | 22.2% | (before curative surgery) | Nishida et al[60] | |
(36 with curative surgery) | 33.3% | (during curative surgery) | |||||
(5 with inoperable) | 80% | (inoperable Pt.) | |||||
I-IV | 57 (PA) | 30 | RT-PCR | CEA mRNA | PA: 17.5% | Miyazono et al[59] | |
49 (PV) | PV: 18.4% | ||||||
51 (SVC) | SVC: 21.6% | ||||||
8.8% | (before surgery) | At least either one positive in PA/PV/SVC | |||||
33.3% | (during surgery) | ||||||
0% | (Ctrl.) | ||||||
EGC, III | 29 (PB) | 15 | RT-PCR | CEA mRNA | EGC: 22.2% | (after surgery) | Noh et al[140] |
(paired, after surgery during surgery and follow-up) | IIIa: 20% | ||||||
IIIb: 26.7% | |||||||
Total: 24.1% | |||||||
EGC: 22.2% | (during follow-up) | ||||||
IIIa: 20% | |||||||
IIIb: 34.4% | |||||||
Total: 34.4% | |||||||
0% | (Ctrl.) | ||||||
I-IV | 106 (PB) | RT-PCR | CEA mRNA | 40.6% | Sumikura et al[141] | ||
(during surgery) | |||||||
I-IV | 41 (PB) | 10 | RT-PCR | CEA mRNA | 24.4% | (Pt.) | Koike et al[142] |
0% | (Ctrl.) | ||||||
I-IV | 46 (PB) (18 EGJ caner)(28 with GC) | 10 (with benign GI disease)100 (tumor-free Ctrl.) | qRT-PCROncoquick density gradient centrifugation | CK20 mRNA | 27.8% | (Pt. with EGJ cancer) | Friederichs et al[143] |
21.4% | (Pt. with GC) | ||||||
0% | (with benign GI disease) | ||||||
1% | (tumor-free Ctrl.) | ||||||
I-IV | 59 (PB) | 15 | qRT-PCR | CEA mRNA | 0% | (before surgery) | Ikeguchi et al[58] |
45.8% | (after surgery) | ||||||
0% | (Ctrl.) | ||||||
I-IV | 70 (PB) | RT-PCR | CK20 mRNA | 36.6% | (Pt. with curative resection) | Illert et al[144] | |
(41 with curative resection) | 44.8% | (Pt. with residual tumor) | |||||
(29 with residual tumor) | Total: 40% | ||||||
I-III | 46 (PB) | 13 | RT-PCR | CEA mRNA | 52.2% | (before surgery) | Seo et al[145] |
(with curative resection) | 19.6% | (after surgery) | |||||
(paired, before and after surgery) | 0% | (Ctrl.) | |||||
I-IV | 52 (PB) | 36 | RT-PCR | c-Met mRNA | 61.5% | (Pt.) | Uen et al[42] |
5.6% | (Ctrl.) | ||||||
MUC1 mRNA | 71.2% | (Pt.) | |||||
8.3% | (Ctrl.) | ||||||
I-IV | 42 (PB) | 30 | RT-PCR | hTERT mRNA | 61.9% | (Pt.) | Wu et al[43] |
0% | (Ctrl.) | ||||||
CK19 mRNA | 69.0% | (Pt.) | |||||
3.3% | (Ctrl.) | ||||||
CK20 mRNA | 61.9% | (Pt.) | |||||
3.3% | (Ctrl.) | ||||||
CEA mRNA | 78.6% | (Pt.) | |||||
0% | (Ctrl.) | ||||||
I-IV | 64 (PB) | 80 | MAH | hTERT mRNA | 81.3% | Wu et al[44] | |
CK19 mRNA | 78.1% | ||||||
CK20 mRNA | 82.8% | ||||||
MUC1 mRNA | 84.4% | ||||||
No detection in controls | |||||||
I-IV | 32 (PB) | FACS/ICC | CK8/18/19 | 21.9% | (before chemotherapy) | Kolodziejczyk et al[146] | |
(paired, before and after chemotherapy) | 15.6% | (after chemotherapy) | |||||
I-IV | 57 (PB) | FACS/ICC | CK8/18/19 | 54.4% | (before surgery) | Pituch-Noworolska et al[61] | |
(before surgery) | 21.2% | (after surgery) | |||||
52 (PB) | |||||||
(after surgery) | 26.8% | (TDB sample) | |||||
56 (TDB) | |||||||
I-IV | 52 (PB) | 20 | qRT-PCR | CEA mRNA | 5.0% | (before surgery) | Tani et al[147] |
(40 pre-ope) | 16.7% | (after surgery) | |||||
(12 post-ope) | |||||||
I-IV | 41 (PB) | 41 | Cell search system | EpCAM | 14.3% | (Nonmetastatic GC) | Hiraiwa et al[55] |
CK8/18/19 | 55.6% | (metastatic GC) | |||||
0% | (Ctrl.) | ||||||
I-IV | 101 (PB) | 14 | qRT-PCR | CK19 mRNA↑ | P = 0.0127 | Curative resection (n = 69) vs Ctrl. (n = 14) | Koga et al[148] |
(69 with curative ope) | P = 0.0087 | Non-curative resection (n = 32) vs Ctrl. (n = 14) | |||||
(32 with non-curative ope) | CK20 mRNA↑ | P = 0.0022 | Non-curative resection (n = 32) vs Ctrl. (n = 14) | ||||
I-IV | 810 (PB) | 29 | RT-PCR | MT1-MMP mRNA | 22.8% | Mimori et al[57] | |
No data for Ctrl. | |||||||
I-IV | 55 (PB) | 86 | RT-PCR ELISA | Survivin mRNA↑ | 45.5% | (Pt.) | Yie et al[149] |
AUC = 0.772 | Pt. (n = 55) vs Ctrl. (n = 86) | ||||||
I-IV | 70 (PB) | 20 | qRT-PCR | CEA mRNA | 45.7% | Bertazza et al[150] | |
CK19 mRNA | 97.1% | ||||||
VEGF mRNA | 38.6% | ||||||
Survivin mRNA | 98.6% | ||||||
(Control samples were used the calibrator source) | |||||||
I-IV | 846 (PB) | 25 | qRT-PCR | uPAR mRNA↑ | 404/846 47.8% | Kita et al[151] | |
P < 0.0001 | Pt. (n = 846) vs Ctrl. (n = 25) | ||||||
Advanced | 52 (PB) | Cell search system | EpCAM | 32.7% | (baseline) | Matsusaka et al[56] | |
(paired, before and during chemotherapy) | CK8/18/19 | 13.7% | (2 wk after chemotherapy) | ||||
18.8% | (4 wk after chemotherapy) | ||||||
I-IV | 123 (PB) | 30 | qRT-PCR | CEA mRNA | 36.6% | (Pt.) | Qiu et al[152] |
30% | (Ctrl.) | ||||||
I-IV | 30 (PB) | qRT-PCR | CK18 mRNA | I/II: 81.8% | Saad et al[153] | ||
(after curative surgery) | III/IV: 31.6% | ||||||
Total: 50% | |||||||
N/A | 90 (PB) | miR-106a↑ | P = 0.006 | Pre-ope vs Ctrl. | Zhou et al[48] | ||
(90 before surgery) | AUC = 0.684 | ||||||
(41 preoperative) | P = 0.016 | Post-ope vs Ctrl. | |||||
(49 postoperative) | miR-17↑ | P = 0.001 | Pre-ope vs Ctrl. | ||||
AUC = 0.743 | |||||||
P = 0.019 | Post-ope vs Ctrl. | ||||||
I-IV | 95 (PB) | 21 | qRT-PCR | B7-H3 mRNA↑ | 50.5% | Arigami et al[154] | |
P < 0.0001 | Pt. (n = 95) vs Ctrl. (n = 21) | ||||||
AUC = 0.86 | |||||||
I-IV | 98 (PB) | 30 | RT-PCR ELISA | Survivin mRNA | I/II: 25% | Cao et al[155] | |
III/IV: 56.1% | |||||||
I-IV: 45.9% | |||||||
I-IV | 93 (PB) | 32 | qRT-PCR | piR-651↓ | P < 0.001 | Pt. (n = 93) vs Ctrl. (n = 32) | Cui et al[49] |
(42 preo-ope) | AUC = 0.841 | ||||||
(51 post-ope) | piR-823↓ | P < 0.001 | |||||
AUC = 0.822 | |||||||
II-IV | 35 (PB) | 50 | qRT-PCR | CEA mRNA | 22.9% | (Pt.) | Dardaei et al[156] |
CK20 mRNA | 37.1% | (Pt.) | |||||
TFF1 mRNA | 31.4% | (Pt.) | |||||
MUC2 mRNA | 22.9% | (Pt.) | |||||
No detection in controls | |||||||
I-IV | 53 (PB) | 20 | qRT-PCR | miR-21↑ | P < 0.0001 | Pt. (n = 53) vs Ctrl. (n = 20) | Zheng et al[50] |
AUC = 0.853 | |||||||
I-IV | 52 (PB) | 15 | qRT-PCR | miR-200c↑ | P = 0.018 | Pt. (n = 52) vs Ctrl. (n = 15) | Valladares-Ayerbes et al[51] |
AUC = 0.715 | |||||||
I-IV | 40 (PB) | 17 | qRT-PCR | miR-421↑ | P < 0.01 | Pt. (n = 40) vs Ctrl. (n = 17) | Zhou et al[52] |
AUC = 0.773 |
Table 2 Prognostic value of circulating tumor cells in gastric cancer
Characteristic and number of patients | Detection method | Statistic value | Ref. | |||||
17 | RT-PCR | CK19 mRNA | OS | P = 0.014 | CK19 (+) vs (-) | Yeh et al[137] | ||
(non-responsive to chemotherapy) | ||||||||
I-IV | 57 | RT-PCR | CEA mRNA | Liver metastasis recurrence | P = 0.03 | CEA (+) vs (-) | (a) | Miyazono et al[59] |
I-IV | 106 | RT-PCR | CEA mRNA | Recurrence/metastasis | P = 0.02 | CEA (+) vs (-) | (a) | Sumikura et al[141] |
I-IV | 46 | qRT-PCR | CK20 mRNA | 2-year-survival | P < 0.05 | CK20 (+) vs (-) | N/A | Friederichs et al[143] |
I-IV | 41 | RT-PCR | CK20 mRNA | OS | P = 0.0363 | CK20 (+) vs (-) | (b) | Illert et al[144] |
(with curative resection) | ||||||||
I-III | 46 | RT-PCR | CEA mRNA | Recurrence | P ≤ 0.00022 | CEA after sugery (+) vs (-) | (a) | Seo et al[145] |
Recurrence | P = 0.015 | (c) | ||||||
I-IV | 52 | RT-PCR | C-Met mRNA | OS | P = 0.0178 | C-Met (+) vs (-) | (b) | Uen et al[42] |
MUC1 mRNA | OS | P = 0.0352 | MUC1 (+) vs (-) | (b) | ||||
I-IV | 42 | RT-PCR | CEA mRNA | Recurrence/metastasis | P = 0.032 | CEA (+) vs (-) | (c) | Wu et al[43] |
I-IV | 64 | MAH | hTERT/CK19/CEA/MUC1 | Recurrence/metastasis | P = 0.009 | All marker (+) vs the others | (c) | Wu et al[44] |
OS | P = 0.0223 | (b) | ||||||
Metastatic | 27 | CellSearch | EpCAM | OS | P = 0.039 | CTC ≥ 2 vs < 2 | (b) | Hiraiwa et al[55] |
System | CK8/18/19 | |||||||
I-IV | 69 | qRT-PCR | CK19 mRNA | OS | P = 0.0347 | CK19 (+) vs (-) | (b) | Koga et al[148] |
(with curative resection) | CK20 mRNA | OS | P = 0.049 | CK20 (+) vs (-) | (b) | |||
I-IV | 810 | RT-PCR | MT1-MMP | Recurrence/metastasis | P = 0.0018 | MT1-MMP (+) vs (-) | (c) | Mimori et al[57] |
I-IV | 55 | RT-PCR ELISA | Survivin mRNA | RFS | P = 0.026 | Survivin (+) vs (-) | (b) | Yie et al[149] |
P = 0.026 | (d) | |||||||
I-IV | 70 | qRT-PCR | Survivin mRNA | OS | P = 0.036 | Survivin high vs low | (b) | Bertazza et al[150] |
P < 0.001 | (d) | |||||||
Advanced | 51 (2 wk after chemotherapy) | Cell search system | EpCAM | PFS (2 wk after chemotherapy) | P < 0.001 | CTC ≥ 4 vs < 4 | (b) | Matsusaka et al[56] |
CK8/18/19 | P < 0.001 | (d) | ||||||
48 (4 wk after chemotherapy) | OS (2 wk after chemotherapy) | P < 0.001 | (b) | |||||
P < 0.001 | (d) | |||||||
PFS (4 wk after chemotherapy) | P < 0.001 | (b) | ||||||
P < 0.001 | (d) | |||||||
OS (4 wk after chemotherapy) | P < 0.001 | (b) | ||||||
P = 0.004 | (d) | |||||||
I-IV | 123 | qRT-PCR | CEA mRNA | Recurrence | P = 0.001 | CEA (+) vs (-) | (a) | Qiu et al[152] |
DFS | P = 0.001 | (b) | ||||||
P = 0.02 | (d) | |||||||
I-IV | 30 | qRT-PCR | CK18 mRNA | RFS | P < 0.001 | CK18 (+) vs (-) | (b) | Saad et al[153] |
(after curative surgery) | P = 0.04 | (d) | ||||||
OS | P = 0.001 | (b) | ||||||
P = 0.06 | (d) | |||||||
I-IV | 95 | qRT-PCR | B7-H3 mRNA | OS | P = 0.02 | B7-H3 high vs low | (b) | Arigami et al[154] |
P = 0.046 | (d) | |||||||
I-IV | 98 | RT-PCR ELISA | Survivin mRNA | DFS | P < 0.001 | Survivin (+) vs (-) | (b) | Cao et al[155] |
P < 0.001 | (d) | |||||||
I-IV | 52 | qRT-PCR | miR-200c | OS | P = 0.016 | miR-200c high vs low | (b) | Valladares-Ayerbes et al[51] |
P = 0.028 | (d) | |||||||
RFS | P = 0.044 | miR-200c high vs low | (b) | |||||
P = 0.028 | (d) |
Table 3 Circulating cell-free DNA in gastric cancer
Characteristic and number of patients | Controls (n) | Plasma/serum | Detection method | Detection rate/statistic value | Ref. | ||||
Unresectable | 198 | 78 (peptic ulcer) | Serum | Immuno-PCR | MG7-Ag | 82.8% | (GC) | Ren et al[157] | |
118 (chronic gastritis) | Semi quantitative | 7.7% | (peptic ulcer) | ||||||
PCR | |||||||||
236 (healthy donors) | 5.9% | (chronic gastritis) | |||||||
0.8% | (healthy donors) | ||||||||
P < 0.01 | Correlation with metastasis | (a) | |||||||
N/A | 51 | 30 (gastritis) | Serum | qPCR | EBV DNA | 100% | (Pt. with EBER (+) | Lo et al[158] | |
in primary tumor) | |||||||||
197 (healthy controls) | 92.9% | (Pt. with EBER (+) | |||||||
in filtrating lymphocytes) | |||||||||
0% | (Pt. with EBER (-) | ||||||||
in primary tumor) | |||||||||
23.3% | (gastritis) | ||||||||
3.6% | (Ctrl.) | ||||||||
I-IV | 54 | 30 | Serum | MSP | DAP-kinase | 48.1% | Lee et al[85] | ||
E-cadherin | 57.4% | ||||||||
GSTP1 | 14.8% | ||||||||
p15 | 55.6% | ||||||||
p16 | 51.9% | ||||||||
No detection in controls | |||||||||
I-IV | 60 | 16 | Serum | MSP | p16 | 26.1% | With p16 methylation | Kanyama et al[159] | |
in primarily tumor | |||||||||
0% | Without p16 methylation | ||||||||
in primarily tumor | |||||||||
0% | (Ctrl.) | ||||||||
I-IV | 109 | 10 | Serum | MSP | p16 | 18.3% | Ichikawa et al[160] | ||
E-cadherin | 23.9% | ||||||||
p16 + E-cadherin | 36.7% | ||||||||
No detection in controls | |||||||||
I-IV | 41 | 10 | Serum | MSP | p16 | 22.0% | Koike et al[142] | ||
E-cadherin | 22.0% | ||||||||
RARb | 14.6% | ||||||||
p16 + E-cadherin + RARb | 24.4% | ||||||||
No detection in controls | |||||||||
I-IV | 63 | 10 | Serum | MSP | p16 | 27.0% | Koike et al[161] | ||
E-cadherin | 23.8% | ||||||||
RARb | 17.5% | ||||||||
p16 + E-cadherin + RARb | 50.8% | ||||||||
No detection in controls | |||||||||
I-IV | 60 | 22 | Serum | qMSP | APC | 16.7% | Leung et al[162] | ||
E-cadherin | 13.3% | ||||||||
hMLH1 | 41.7% | ||||||||
TIMP3 | 16.7% | ||||||||
Four markers combined | 55% | ||||||||
13.6% | (Ctrl.) | ||||||||
APC + E-cadherin | OS: P = 0.006 | Methylation (+) vs (-) | (b) | ||||||
I-IV | 109 | 10 | Serum | MSP | RARb | 23.8% | Ikoma et al[163] | ||
p16 + E-cadherin + RARb | 47.7% | ||||||||
I-IV | 53 | 21 | Plasma | qPCR | β-actin (102 bp) | P = 0.03 | Pt.(n = 53) vs Ctrl. (n = 21) | (c) | Sai et al[83] |
β-actin (253 bp) | P < 0.0001 | (c) | |||||||
AUC = 0.75 | |||||||||
DNA integrity (253 bp/102 bp) | P = 0.07 | (c) | |||||||
N/A | 4 | 10 | Serum | MSP | RUNX3 | 100% | Tan et al[164] | ||
p16 | 50% | ||||||||
RASSF1A | 25% | ||||||||
CDH1 | 25% | ||||||||
No detection in controls | |||||||||
I-IV | 52 | 20 | Serum | MSP | p16 | 9.6% | Tani et al[147] | ||
(40 pre-ope) | E-cadherin | 9.6% | |||||||
(12 post-ope) | RARb | 3.8% | |||||||
p16 + E-cadherin + RARb | 23.1% | ||||||||
I-IV | 52 | 50 | Serum | MSP | p16 | 26.9% | (all Pt.) | Abbaszadegan et al[165] | |
60.9% | (Pt. with p16 methylation in primary tumor) | ||||||||
0% | (Ctrl.) | ||||||||
I-IV | 20 | 22 | Plasma | Fluorescence-based assay | DNA concentration↑ | P < 0.005 | Pt.(n = 20) vs Ctrl. (n = 22) | (d) | Kolesnikova et al[166] |
MSP | MGMT | 70% | (Pt.) | ||||||
36.4% | (Ctrl.) | ||||||||
p15 | 50% | (Pt.) | |||||||
18.2% | (Ctrl.) | ||||||||
hMLH1 | 25% | (Pt.) | |||||||
9.1% | (Ctrl.) | ||||||||
I-IV | 47 | 30 (benign gastric disease) | Serum | MSP | RASSF1A | 24.0% | (Pt.) | Wang et al[167] | |
30 (healthy controls) | 3.3% | (benign gastric disease) | |||||||
0% | (healthy controls) | ||||||||
I-IV | 20 | 21 | Serum | MSP | HSulf-1 | 55% | (Pt.) | Chen et al[168] | |
19.0% | (Ctrl.) | ||||||||
I-IV | 57 | 79 | Plasma | qPCR | MYC/GAPDH↑ | P < 0.001 | Pt. (n = 57) vs Ctrl. (n = 79) | Park et al[91] | |
AUC = 0.841 | |||||||||
I-IV | 65 | 50 | Serum | qMSP | RUNX3 | 29.2% | (Pt.) | Sakakura et al[169] | |
10% | (Ctrl.) | ||||||||
AUC = 0.8651 | Pt. (n = 65) vs Ctrl. (n = 50) | ||||||||
I-IV | 65 | 40 (benign gastric disease) | Serum | MSP | DLEC1 | 33.8% | (Pt.) | Zhang et al[170] | |
20 (healthy controls) | 5% | (benign gastric disease) | |||||||
0% | (healthy controls) | ||||||||
I-IV | 73 | 20 | Serum | qMSP | TFPI2 | 9.6% | (Pt.) | Hibi et al[171] | |
0% | (Ctrl.) | ||||||||
P = 0.004 | Correlation with LN meta. | (a) | |||||||
P = 0.0115 | Correlation with distant meta. | (a) | |||||||
I-IV | 65 | 80 | Plasma | qMSP | SLC19A3 | P < 0.0001 | Pt.(n = 45) vs Ctrl. (n = 60) | Ng et al[172] | |
(Validation 1) | |||||||||
AUC = 0.82 | Pt. (n = 20) vs Ctrl. (n = 20) | ||||||||
(Validation 2) | |||||||||
I-IV | 46 | 30 (healthy controls) | Serum | Methylation CpG island microarray | BX141696 | 56.5% | Zheng et al[86] | ||
46 (benign gastric disease) | MSP | WT1 | 50% | ||||||
CYP26B1 | 73.9% | ||||||||
KCNA4 | 67.4% | ||||||||
I-IV | 58 | 30 (healthy controls) | Serum | MeDIP | CHRM2 | 31.0% | Chen et al[87] | ||
46 (gastric precancerous lesions) | Methylation CpG island microarray | FAM5C | 31.0% | ||||||
MSP | P < 0.001 | Pre- vs post-operation | |||||||
MYLK | 70.7% | ||||||||
P < 0.001 | Pre- vs post-operation | ||||||||
FAM5C + MYLK | 77.6% | (GC Pt.) | |||||||
10% | (healthy controls) | ||||||||
30.4% | (gastric precancerous lesions) | ||||||||
I-IV | 59 | 54 | Plasma | qPCR | ALU↑ | P < 0.001 | Pt. (n = 59) vs Ctrl. (n = 54) | (c) | Park et al[84] |
AUC = 0.784 | |||||||||
N/A | 25 | 9 | Plasma | MSP | ATP4B | 64% | (Pt.) | Raja et al[173] | |
0% | (Ctrl.) | ||||||||
I-IV | 71 | 21 | Serum | qMSP | Vimentin | P = 0.018 | Pt. (n = 73) vs Ctrl. (n = 21) | (c) | Shirahata et al[174] |
Operable | 73 | 20 | Serum | MSP | SOX17 | 58.9% | (Pt.) | Balgkouranidou et al[175] | |
0% | (Ctrl.) | ||||||||
OS: P = 0.049 | Methylation (+) vs (-) | (b) | |||||||
I-IV | 73 | Plasma | qPCR | HER2 | 64.4% | Pt. with 2+/3+ score in HER2 IHC assay | Lee et al[92] | ||
Pt. with 2+/3+ score in HER2 IHC assay | |||||||||
I-IV | 202 | 88 | Serum | qMSP | XAF1 | 69.8% | (Pt.) | Ling et al[88] | |
0% | (Ctrl.) | ||||||||
AUC = 0.909 | Pt. (n = 202) vs Ctrl.(n = 88) | ||||||||
DFS: P < 0.0001 | Methylation (+) vs (-) | (b) |
Table 4 Circulating cell-free mRNA in gastric cancer
Characteristic and number of patients | Controls (n) | Plasma/serum | Detection method | Detection rate/statistic value | Ref. | ||||
I-IV | 52 | 20 | Plasma | qRT-PCR | hTERT | 7.5% | (preoperative) | Tani et al[147] | |
(40 preoperative) | MUC1 | 1% | |||||||
(12 postoperative) | hTERT + MUC1 | 15% | |||||||
hTERT | 16.7% | (postoperative) | |||||||
MUC1 | 8.3% | ||||||||
hTERT + MUC1 | 16.7% | ||||||||
No detection in controls | |||||||||
I-IV | 89 | 42 | Plasma | qRT-PCR | CXCR4↑ | 41.6% | [before surgery (n = 89)] | Xu et al[176] | |
[paired, before and | 23.2% | [after surgery (n = 69)] | |||||||
after surgery (n = 69)] | 21.4% | [Ctrl. (n = 42)] | |||||||
P < 0.05 | Before surgery (n = 89) vs Ctrl. (n = 42) | (a) | |||||||
Bmi-1↑ | 57.3% | [before surgery (n = 89)] | |||||||
43.5% | [after surgery (n = 69)] | ||||||||
28.6% | [Ctrl. (n = 42)] | ||||||||
P < 0.05 | Before surgery (n = 89) vs Ctrl. (n = 42) | (a) | |||||||
P < 0.05 | Before (n = 89) vs after (n = 69) surgery | (a) | |||||||
I-IV | 118 | 40 (gastritis) | Plasma | qRT-PCR | hTERT mRNA↑ | P < 0.05 | GC (n = 118) vs gastritis (n = 40) | (a) | Kang et al[123] |
58 (healthy controls) | P < 0.05 | GC (n = 118) vs Ctrl. (n = 58) | (a) | ||||||
AUC = 0.891 | GC (n = 118) vs Ctrl. (n = 58) | ||||||||
DFS: P < 0.001 | (b) | ||||||||
DFS: P = 0.001 | (c) | ||||||||
OS: P < 0.001 | (b) | ||||||||
OS: P < 0.001 | (c) |
Table 5 Circulating cell-free microRNA/long non-coding RNA in gastric cancer
Characteristic and number of patients | Controls (n) | Plasma/serum | Detection method | Detection rate/statistic value | Ref. | |||||
microRNA | ||||||||||
I-IV | 69 | 30 | Plasma | qRT-PCR | miR-17-5p↑ | P = 0.05 | Pt. (n = 69) vs Ctrl (n = 30) | (a) | Tsujiura et al[124] | |
miR-21↑ | P = 0.006 | Pt. (n = 69) vs Ctrl (n = 30) | (a) | |||||||
P = 0.013 | paired (n = 10), pre-op > post-op | (b) | ||||||||
miR-106a↑ | P = 0.008 | Pt. (n = 69) vs Ctrl (n = 30) | (a) | |||||||
miR-106b↑ | P < 0.001 | AUC = 0.721 | Pt. (n = 69) vs Ctrl (n = 30) | (a) | ||||||
P = 0.022 | paired (n = 10), pre-op > post-op | (b) | ||||||||
let-7a↓ | P = 0.002 | Pt. (n = 69) vs Ctrl (n = 30) | (a) | |||||||
miR-106a/let-7a↑ | AUC = 0.879 | |||||||||
I-IV | 164 | 127 | Serum | Solexa sequencing | miR-1↑ | P < 0.01 | Pt. (n = 164) vs Ctrl (n = 127) | (a) | Liu et al[177] | |
qRT-PCR | miR-20a↑ | P < 0.01 | (a) | |||||||
miR-27a↑ | P < 0.01 | (a) | ||||||||
miR-34a↑ | P < 0.01 | (a) | ||||||||
miR-423-5p↑ | P < 0.01 | (a) | ||||||||
Five-serum miRNA signature↑ | AUC = 0.879 | Pt. (n = 22) vs Ctrl (n = 22) (test study) | ||||||||
AUC = 0.831 | Pt. (n = 142) vs Ctrl (n = 105) (validation study) | |||||||||
I-IV | 56 | 30 | Plasma | Microarray | miR-451↑ | P < 0.01 | AUC = 0.96 | Pt. (n = 56) vs Ctrl (n = 30) | (a) | Konishi et al[125] |
qRT-PCR | P < 0.01 | paired (n = 29), pre-op > post-op | (b) | |||||||
miR-486↑ | P < 0.01 | AUC = 0.92 | Pt. (n = 56) vs Ctrl (n = 30) | (a) | ||||||
P < 0.01 | paired (n = 29), pre-op > post-op | (b) | ||||||||
I-IV | 40 | 41 | Serum | Microarray | miR-187*↑ | P = 0.0016 | AUC = 0.704 | Pt. (n = 40) vs Ctrl (n = 41) | (a) | Liu et al[178] |
qRT-PCR | miR-371-5p↑ | P = 0.0009 | AUC = 0.715 | (a) | ||||||
miR-378↑ | P < 0.0001 | AUC = 0.861 | (a) | |||||||
N/A | 82 | 82 | Serum | Microarray | miR-221↑ | AUC = 0.74 | Pt. (n = 68) vs Ctrl (n = 68) (second validation study) | Song et al[179] | ||
qRT-PCR | miR-376c↑ | AUC = 0.71 | ||||||||
miR-744↑ | AUC = 0.71 | |||||||||
N/A | 20 | Serum | qRT-PCR | miR-196a | P = 0.012 | Pre-op (n = 20) > post-op (n = 20) | (a) | Tsai et al[180] | ||
(pre-op, post-op and recurrent) | P = 0.002 | Post-op (n = 20) < at recurrent (n = 20) | (a) | |||||||
I-IV | 30 | 39 | Serum | qRT-PCR | miR-21↑ | P < 0.001 | AUC = 0.81 | Pt. (n = 30) vs Ctrl (n = 39) | (a) | Wang et al[181] |
I-IV | 87 | Plasma | qRT-PCR | miR-17-5p↑ | P < 0.001 | Pre-op (n = 65) > post-op (n = 16) | (a) | Wang et al[182] | ||
(65 pre-op) | P = 0.003 | Post-op (n = 16) < recurrent (n = 6) | (a) | |||||||
(16 post-op) | OS: P = 0.0003 | miR-17-5p high vs low | Pre-op (n = 65) | (c) | ||||||
(6 recurrent) | miR-20a↑ | P = 0.006 | Pre-op (n = 65) > post-op (n = 16) | (a) | ||||||
OS: P = 0.0003 | miR-20a high vs low | Pre-op (n = 65) | (c) | |||||||
OS: P = 0.013 | miR-20a high vs low | pre-op (n = 65) | (d) | |||||||
I-IV | 20 | 20 | Serum | miRNA microarray | miR-375↓ | P < 0.001 | AUC = 0.835 | Pt. (n = 20) vs Ctrl (n = 20) | (a) | Zhang et al[183] |
qRT-PCR | ||||||||||
20 | 190 | Plasma | miRNA microarray | miR-195-5p↓ | P < 0.05 | Fold changes 13.3 | Pt. (n = 20) vs Ctrl (n = 130) | (a) | Gorur et al[184] | |
I-III | 79 | miR-21↑ | P < 0.001 | Correlation with pN stage | (e) | Kim et al[185] | ||||
(25 without LN meta) | miR-146a↑ | P = 0.001 | Correlation with pN stage | (e) | ||||||
(54 with LN meta) | miR-148a↑ | P < 0.001 | Correlation with pN stage | (e) | ||||||
I-IV | 69 | Plasma | qRT-PCR | miR-21↑ | CSS: P = 0.0451 | miR-21 high vs low | (c) | Komatsu et al[186] | ||
CSS: P = 0.0133 | (d) | |||||||||
I-II | 80 | 70 | Plasma | qRT-PCR | miRNA-199a-3p↑ | P < 0.001 | AUC = 0.818 | Pt. (n = 80) vs Ctrl. (n = 70) | (a) | Li et al[187] |
(healthy controls) | P = 0.004 | Pt. (n = 80) vs pancreous disease (n = 20) | (a) | |||||||
20 | P = 0.012 | Pre-op > post-op (n = 30) | (b) | |||||||
(precancerous disease) | ||||||||||
Long non-coding RNA | ||||||||||
I-IV | 43 | 33 | Plasma | qRT-PCR | H19 | P = 0.029 | Pt. (n = 43) vs Ctrl. (n = 33) | (a) | Arita et al[128] | |
HOTAIR | P = 0.096 | (a) | ||||||||
MALAT1 | P = 0.14 | (a) |
- Citation: Tsujiura M, Ichikawa D, Konishi H, Komatsu S, Shiozaki A, Otsuji E. Liquid biopsy of gastric cancer patients: Circulating tumor cells and cell-free nucleic acids. World J Gastroenterol 2014; 20(12): 3265-3286
- URL: https://www.wjgnet.com/1007-9327/full/v20/i12/3265.htm
- DOI: https://dx.doi.org/10.3748/wjg.v20.i12.3265