Molecular alterations and clinical relevance in esophageal squamous cell carcinoma
Molecular alterations and clinical relevance in esophageal squamous cell carcinoma
Li Shang, Mingrong Wang()
State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China
Esophageal squamous cell carcinoma (ESCC) is one of the most common types of gastrointestinal cancers, and the fourth leading cause of cancer-related deaths in China. Early detection and intervention in time may dramatically increase the survival of the patients by initiating treatment regimens during earlier stages of ESCC or even during precancerous stages. Molecular classification will be useful for subtyping esophageal tumors or precancerous lesions to improve current therapeutics or early intervention of the disease. In this review, we summarize the findings in investigating the molecular alterations and clinical relevance of ESCC.
EC patients and individuals of high-incidence area of EC tissue
503
FC, qRT-PCR
↓
MCM2
Linzhou, China [17]
ESCC and precancerous lesions
299
IHC
↑
P53
Brazi [43]
Asymptomatic individuals at high risk for ESCC
202
IHC
↑
China [44]
ESCC and precancerous lesions
109
IHC
↑
Japan [45]
Biopsy specimens
105
IHC
↑
Japan [46]
ESCC and precancerous lesions
72
IHC
↑
pRB
Brazi [47]
Asymptomatic individuals at high risk for ESCC
190
IHC
↑
Japan [45]
Biopsy specimens
105
IHC
↑
Plant-associated human cancer antigen
Bejing, China [48]
Biopsy specimens of ESCC and precancerous lesions
174
IHC
↑
FHIT
Korea [49]
Stage 1-2 ESCC tissue
138
MSP, IHC
Hypermethylation
PTCH1
Bejing, China [50]
Pre-treatment serum of ESCC and precancerous lesions tissue
137
IHC
↑
Esophagin
USA [51]
ESCC and precancerous lesions
91
IHC
↓
PCNA
USA [51]
ESCC and precancerous lesions
91
IHC
↑
ALCAM
Hamburg, Germany [52]
Stage I ESCC tissue
64
IHC
↑
ECT2
Japan [53]
pT1 ESCC tissue
52
cDNA microarray, IHC
↑
POLB
Linzhou, China [54]
ESCC tissue
51
ISH, IHC
↑
Eight microsatellite loci
ChongqingChina [12]
ESCC and precancerous lesions
34
PCR-based LOH
LOH
Tab.1
Name
Population
Specimen type
Case
ROC AUC
95% CI
Sensitivity
Specificity
miR-1322
Henan, China [29]
Serum
402
0.847
0.795-0.890
81.7%
82.5%
miR-31
Henan, China [28]
Serum
446
0.902
0.857-0.936
86.7%
84.3%
LY6K and CYFRA 21-1
Japan [15]
Serum
81
-
-
52.5%
-
OIP5
Japan [16]
ESCC tissue
305
-
-
58.4%
100%
MCM2
Linzhou, China [17]
ESCC and precancerous lesions
299
-
-
91.3%
61.8%
DKK1
Japan [24]
Serum
81
-
-
63.0%
-
STC1
Japan [55]
ESCC tissue
229
-
-
38.9%
100%
PKM2
Xinjiang, China [56]
ESCC tissue
175
-
-
74.9%
90.3%
Synuclein-gamma
China [57]
Pre-treatment serum of ESCC
-
-
-
19.5%
98.7%
3, 8, 10, 20 chromosome
Bejing, China [9]
ESCC tissue
246
-
-
74.5%
-
ABCC3
Bejing, China [58]
Serum
340
-
-
>95.0%
13.2%
MMP-7
Hebei, China [59]
Serum
108
0.87
0.80-0.93
78.0%
81.0%
FOXP3
Shanghai, China [60]
ESCC tissue
112
-
-
71.4%
78.4%
MMP-9
Bejing, China [61]
ESCC tissue
208
-
-
49.0%
100%
Tab.2
Name
Case
Methods
Study population
Hazard ration
95% confidence interval
Unfavorable/favorable
P-value
Analytic method
LY6K [15]
265
IHC
Stage1-4
1.480
1.041-2.105
Strong (+)/weak(+) or (-)
0.0289
Univariate analysis
OIP5 [16]
305
IHC
Stage1-4
1.560
1.080-2.254
Positive/negative
0.0177
Univariate analysis
ET [23]
108
ELISA
Stage1-4
2.494
1.302-3.806
Elevated/normal
0.002
Univariate analysis for predictors of OS
DKK1 [24]
280
IHC
Stage1-4
-
-
Strong/absent
0.022
Kaplan-Meier analysis of survival
STC1 [55]
229
IHC
Stage1-4
-
-
Positive/negative
0.0006
Kaplan-Meier analysis of survival
FHIT methylation [49]
138
MSP
Stage1-2
5.81
1.15-14.07
Yes/no
0.009
Stratified Kaplan-Meier analysis of survival
ALCAM [52]
146
IHC
Stage1-4
12.3
10.1-14.5
Positive/negative
0.012
Log-rank OS analysis
ECT2 [53]
240
IHC
Stage1-4
2.477
1.470-4.175
Strong(+)/weak(+) or (-)
0.0093
Univariate analysis
AEG-1 [62]
168
IHC
Stage1-4
-
-
Higher/lower
0.004
Log-rank test
L1/LINE-1 [63]
217
bisulfite pyrosequencing
Stage1-4
2.32
1.38-3.84
Hypomethylation/highmethylation
0.0017
Univariate analyses for cancer-specific survival
RKIP [64]
274
IHC
Stage1-4
-
-
Reduced/positive
0.004
Kaplan-Meier analysis of survival
USP22 [65]
157
IHC
stage 2b-3
-
-
Higher/lower
0.029
Stratified Kaplan-Meier analysis of survival
DBC1 [66]
199
IHC
Stage1-4
2.889
-
Higher/lower
<0.001
Univariate analysis
Twist1 [67]
199
IHC, RT-PCR
Stage1-4
3.019
-
Positive/negative
0.000
Univariate analysis
Cyr61 [68]
212
IHC
Stage1-2
-
-
High/low
0.001
Stratified Kaplan-Meier analysis of survival
ULK1 [69]
248
IHC
pT3-4
-
-
High/low
0.001
Stratified Kaplan-Meier analysis of survival
claudin-4 [70]
164
IHC
Stage1-4
-
-
Low/high
0.0009
Kaplan-Meier analysis of survival
HGF [71]
149
ELISA
Stage1-4
-
-
High/low
0.0137
Kaplan-Meier analysis of survival
E-cadherin [72]
203
IHC
Stage1-4
-
-
preserved/reduced
0.0049
Univariate analysis
Cyclin D1 [73]
148
IHC
Stage1-4
2.198
1.384-3.49
Positive/negative
0.001
Univariate analysis
P53 [74]
100
IHC
Stage1-4
-
-
With overexpressed/without
0.0001
Kaplan-Meier analysis of survival
VEGF [75]
112
IHC
Stage1-4
-
-
Positive/negative
0.038
Kaplan-Meier analysis of survival
COX2 [76]
110
IHC
Stage1-4
-
-
Positive/negative
0.0036
Kaplan-Meier analysis of survival
EGFR [77]
110
IHC
Stage1-4
-
-
Strong/weak
0.0028
Kaplan-Meier analysis of survival
Laminin-5 gamma 2 [77]
110
IHC
Stage1-4
-
-
Positive/negative
0.001
Kaplan-Meier analysis of survival
Tab.3
Name
Case
Methods
Hazard ration
95% confidence interval
Unfavorable/favorable
P-value
ET [23]
108
ELISA
2.629
1.375-4.054
Elevated/normal
0.003
STC1 [55]
229
IHC
1.6841
1.116-2.620
Positive/negative
0.0162
L1/LINE-1 [63]
217
Bisulfite pyrosequencing
1.81
1.060-3.050
Hypomethylation/highmethylation
0.031
DBC1 [66]
199
IHC
2.655
-
Higher/lower
<0.001
Twist1 [67]
199
IHC, RT-PCR
3.131
-
Positive/negative
0.000
ULK1 [69]
248
IHC
2.220
1.434-3.436
High/low
<0.001
HGF [71]
149
ELISA
1.0009
1.0005-1.0014
High/low
0.0001
Cyclin D1 [78]
416
IHC
1.42
1.04-1.94
Positive/negative
0.028
E-cadherin [79]
106
IHC
0.65
0.456-0.926
0/1/2
0.017
P53 [80]
258
ELISA
10.6
2.76-40.00
+/ -
<0.001
VEGF [81]
120
ELISA
3.832
-
High/low
<0.001
COX2 [82]
110
IHC
-
-
High/low
0.000
CRP [80]
258
ELISA
5.05
1.56-16.39
High/low
0.007
Laminin-5 gamma 2 [83]
100
IHC
2.6
1.4-4.7
Positive/negative
0.0028
SCC antigen [84]
215
ELISA
1.87
1.19-2.95
High/low
<0.01
CXCR4 [85]
136
IHC
2.18
1.33-3.59
Positive/negative
0.002
Fascin [86]
200
IHC
1.79
1.15-2.77
Weak/moderate/strong
0.0094
HGF [71]
149
ELISA
1.0009
1.0005-1.0014
>Median/≤median
0.0001
Tab.4
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