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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2013, Vol. 7 Issue (4) : 401-410    https://doi.org/10.1007/s11684-013-0286-y
REVIEW
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
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Abstract

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.

Keywords esophageal squamous cell carcinoma (ESCC)      early detection      molecular classification      molecular markers     
Corresponding Author(s): Wang Mingrong,Email:wangmr2015@126.com   
Issue Date: 05 December 2013
 Cite this article:   
Li Shang,Mingrong Wang. Molecular alterations and clinical relevance in esophageal squamous cell carcinoma[J]. Front Med, 2013, 7(4): 401-410.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-013-0286-y
https://academic.hep.com.cn/fmd/EN/Y2013/V7/I4/401
NamePopulationSpecimen typeCaseMethodsAlteration
HLA-I on PBMCsShandong, China [42]EC patients and individuals of high-incidence area of EC tissue503FC, qRT-PCR
MCM2Linzhou, China [17]ESCC and precancerous lesions299IHC
P53Brazi [43]Asymptomatic individuals at high risk for ESCC202IHC
China [44]ESCC and precancerous lesions109IHC
Japan [45]Biopsy specimens105IHC
Japan [46]ESCC and precancerous lesions72IHC
pRBBrazi [47]Asymptomatic individuals at high risk for ESCC190IHC
Japan [45]Biopsy specimens105IHC
Plant-associated human cancer antigenBejing, China [48]Biopsy specimens of ESCC and precancerous lesions174IHC
FHITKorea [49]Stage 1-2 ESCC tissue138MSP, IHCHypermethylation
PTCH1Bejing, China [50]Pre-treatment serum of ESCC and precancerous lesions tissue137IHC
EsophaginUSA [51]ESCC and precancerous lesions91IHC
PCNAUSA [51]ESCC and precancerous lesions91IHC
ALCAMHamburg, Germany [52]Stage I ESCC tissue64IHC
ECT2Japan [53]pT1 ESCC tissue52cDNA microarray, IHC
POLBLinzhou, China [54]ESCC tissue51ISH, IHC
Eight microsatellite lociChongqingChina [12]ESCC and precancerous lesions34PCR-based LOHLOH
Tab.1  Early molecular alterations in esophageal squamous cell carcinoma (ESCC)
NamePopulationSpecimen typeCaseROC AUC95% CISensitivitySpecificity
miR-1322Henan, China [29]Serum4020.8470.795-0.89081.7%82.5%
miR-31Henan, China [28]Serum4460.9020.857-0.93686.7%84.3%
LY6K and CYFRA 21-1Japan [15]Serum81--52.5%-
OIP5Japan [16]ESCC tissue305--58.4%100%
MCM2Linzhou, China [17]ESCC and precancerous lesions299--91.3%61.8%
DKK1Japan [24]Serum81--63.0%-
STC1Japan [55]ESCC tissue229--38.9%100%
PKM2Xinjiang, China [56]ESCC tissue175--74.9%90.3%
Synuclein-gammaChina [57]Pre-treatment serum of ESCC---19.5%98.7%
3, 8, 10, 20 chromosomeBejing, China [9]ESCC tissue246--74.5%-
ABCC3Bejing, China [58]Serum340-->95.0%13.2%
MMP-7Hebei, China [59]Serum1080.870.80-0.9378.0%81.0%
FOXP3Shanghai, China [60]ESCC tissue112--71.4%78.4%
MMP-9Bejing, China [61]ESCC tissue208--49.0%100%
Tab.2  Potential diagnosis markers for diagnosis of esophageal squamous cell carcinoma (ESCC)
NameCaseMethodsStudy populationHazard ration95% confidence intervalUnfavorable/favorableP-valueAnalytic method
LY6K [15]265IHCStage1-41.4801.041-2.105Strong (+)/weak(+) or (-)0.0289Univariate analysis
OIP5 [16]305IHCStage1-41.5601.080-2.254Positive/negative0.0177Univariate analysis
ET [23]108ELISAStage1-42.4941.302-3.806Elevated/normal0.002Univariate analysis for predictors of OS
DKK1 [24]280IHCStage1-4--Strong/absent0.022Kaplan-Meier analysis of survival
STC1 [55]229IHCStage1-4--Positive/negative0.0006Kaplan-Meier analysis of survival
FHIT methylation [49]138MSPStage1-25.811.15-14.07Yes/no0.009Stratified Kaplan-Meier analysis of survival
ALCAM [52]146IHCStage1-412.310.1-14.5Positive/negative0.012Log-rank OS analysis
ECT2 [53]240IHCStage1-42.4771.470-4.175Strong(+)/weak(+) or (-)0.0093Univariate analysis
AEG-1 [62]168IHCStage1-4--Higher/lower0.004Log-rank test
L1/LINE-1 [63]217bisulfite pyrosequencingStage1-42.321.38-3.84Hypomethylation/highmethylation0.0017Univariate analyses for cancer-specific survival
RKIP [64]274IHCStage1-4--Reduced/positive0.004Kaplan-Meier analysis of survival
USP22 [65]157IHCstage 2b-3--Higher/lower0.029Stratified Kaplan-Meier analysis of survival
DBC1 [66]199IHCStage1-42.889-Higher/lower<0.001Univariate analysis
Twist1 [67]199IHC, RT-PCRStage1-43.019-Positive/negative0.000Univariate analysis
Cyr61 [68]212IHCStage1-2--High/low0.001Stratified Kaplan-Meier analysis of survival
ULK1 [69]248IHCpT3-4--High/low0.001Stratified Kaplan-Meier analysis of survival
claudin-4 [70]164IHCStage1-4--Low/high0.0009Kaplan-Meier analysis of survival
HGF [71]149ELISAStage1-4--High/low0.0137Kaplan-Meier analysis of survival
E-cadherin [72]203IHCStage1-4--preserved/reduced0.0049Univariate analysis
Cyclin D1 [73]148IHCStage1-42.1981.384-3.49Positive/negative0.001Univariate analysis
P53 [74]100IHCStage1-4--With overexpressed/without0.0001Kaplan-Meier analysis of survival
VEGF [75]112IHCStage1-4--Positive/negative0.038Kaplan-Meier analysis of survival
COX2 [76]110IHCStage1-4--Positive/negative0.0036Kaplan-Meier analysis of survival
EGFR [77]110IHCStage1-4--Strong/weak0.0028Kaplan-Meier analysis of survival
Laminin-5 gamma 2 [77]110IHCStage1-4--Positive/negative0.001Kaplan-Meier analysis of survival
Tab.3  Molecular alterations associated with prognosis of ESCC patients
NameCaseMethodsHazard ration95% confidence intervalUnfavorable/favorableP-value
ET [23]108ELISA2.6291.375-4.054Elevated/normal0.003
STC1 [55]229IHC1.68411.116-2.620Positive/negative0.0162
L1/LINE-1 [63]217Bisulfite pyrosequencing1.811.060-3.050Hypomethylation/highmethylation0.031
DBC1 [66]199IHC2.655-Higher/lower<0.001
Twist1 [67]199IHC, RT-PCR3.131-Positive/negative0.000
ULK1 [69]248IHC2.2201.434-3.436High/low<0.001
HGF [71]149ELISA1.00091.0005-1.0014High/low0.0001
Cyclin D1 [78]416IHC1.421.04-1.94Positive/negative0.028
E-cadherin [79]106IHC0.650.456-0.9260/1/20.017
P53 [80]258ELISA10.62.76-40.00+/ -<0.001
VEGF [81]120ELISA3.832-High/low<0.001
COX2 [82]110IHC--High/low0.000
CRP [80]258ELISA5.051.56-16.39High/low0.007
Laminin-5 gamma 2 [83]100IHC2.61.4-4.7Positive/negative0.0028
SCC antigen [84]215ELISA1.871.19-2.95High/low<0.01
CXCR4 [85]136IHC2.181.33-3.59Positive/negative0.002
Fascin [86]200IHC1.791.15-2.77Weak/moderate/strong0.0094
HGF [71]149ELISA1.00091.0005-1.0014>Median/≤median0.0001
Tab.4  Molecular alterations as independent factor for prognosis of ESCC patients detected by multivariate analysis with Coxproportional hazards model
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