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pmid:34249086

Identification of an EMT-Related Gene Signature for Predicting Overall Survival in Gastric Cancer.

Weiyu Dai · Yizhi Xiao · Weimei Tang · Jiaying Li · Linjie Hong · Jieming Zhang · Miaomiao Pei · Jianjiao Lin · Side Liu · Xiaosheng Wu · Li Xiang · Jide Wang

Frontiers in genetics · 2021 doi:10.3389/fgene.2021.661306

Paper

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Data

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title
Identification of an EMT-Related Gene Signature for Predicting Overall Survival in Gastric Cancer.
doi
10.3389/fgene.2021.661306
pmid
34249086
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[0]
Weiyu Dai
[1]
Yizhi Xiao
[2]
Weimei Tang
[3]
Jiaying Li
[4]
Linjie Hong
[5]
Jieming Zhang
[6]
Miaomiao Pei
[7]
Jianjiao Lin
[8]
Side Liu
[9]
Xiaosheng Wu
[10]
Li Xiang
[11]
Jide Wang
journal
Frontiers in genetics
year
2021
abstract
BACKGROUND: It has been widely reported that epithelial-mesenchymal transition (EMT) is associated with malignant progression in gastric cancer (GC). Integration of the molecules related to EMT for predicting overall survival (OS) is meaningful for understanding the role of EMT in GC. Here, we aimed to establish an EMT-related gene signature in GC. METHODS: Transcriptional profiles and clinical data of GC were downloaded from The Cancer Genome Atlas (TCGA). We constructed EMT-related gene signature for predicting OS by using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. Time-dependent receiver operating characteristic (ROC), Kaplan-Meier analysis were performed to assess its predictive value. A nomogram combining the prognostic signature with clinical characteristics for OS prediction was established. And its predictive power was estimated by concordance index (C-index), time-dependent ROC curve, calibration curve and decision curve analysis (DCA). GSE62254 dataset from Gene Expression Omnibus (GEO) was used for external validation. Quantitative real-time PCR (qRT-PCR) was used to detected the mRNA expression of the five EMT-related genes in human normal gastric mucosal and GC cell lines. To further understand the potential mechanisms of the signature, Gene Set Enrichment Analysis (GSEA), pathway enrichment analysis, predictions of transcription factors (TFs)/miRNAs were performed. RESULTS: A novel EMT-related gene signature (including ITGAV, DAB2, SERPINE1, MATN3, PLOD2) was constructed for OS prediction of GC. With external validation, ROC curves indicated the signature's good performance. Patients stratified into high- and low-risk groups based on the signature yielded significantly different prognosis. Univariate and multivariate Cox regression suggested that the signature was an independent prognostic variable. Nomogram for prognostication including the signature presented better predictive accuracy and clinical usefulness than the similar model without risk score to some extent with external validation. The qRT-PCR assays suggested that high expression of the five EMT-related genes could be found in human GC cell lines compared with normal gastric mucosal cell line. GSEA and pathway enrichment analysis revealed that focal adhesion and ECM-receptor interaction might be the two important pathways to the signature. CONCLUSION: Our EMT-related gene signature may have practical application as an independent prognostic factor in GC.
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sections[13] "Survival Analysis" paragraph 2
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All the survival analyses mentioned above were performed by Kaplan-Meier curve with a two-side log-rank test.
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Publicly available datasets were analyzed in this study. This data can be found here: TCGA database: https://portal.gdc.cancer.gov/; GEO database: https://www.ncbi.nlm.nih.gov/geo/.
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sections[24] "Data Availability Statement" paragraph 2
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Publicly available datasets were analyzed in this study. This data can be found here: TCGA database: https://portal.gdc.cancer.gov/; GEO database: https://www.ncbi.nlm.nih.gov/geo/.
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Molecular analysis of gastric cancer identifies discrete subtypes associated with distinct clinical characteristics and survival outcomes: the ACRG (Asian Cancer Research Group) study [gastric tumors]
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EMT-Related Gene Signature in Different Clinical Subgroups
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table object · 8 fields
label
TABLE 2
caption
Univariate and multivariate Cox regression analyses of clinical characteristics and risk score in GSE62254.
rows array · 20 items
[0] array · 4 items
[0]
[1]
[2]
Univariate Cox
[3]
Multivariate Cox
[1] array · 4 items
[0]
[1]
[2]
regression
[3]
regression
[2] array · 6 items
[0]
Characteristics
[1]
Number
[2]
Hazard Ratio (95%CI)
[3]
p-value
[4]
Hazard Ratio (95%CI)
[5]
p-value
[3] array · 6 items
[0]
Age
[1]
298
[2]
1.011 (0.996–1.026)
[3]
0.157
[4]
1.028 (1.012–1.044)
[5]
0.001
[4] array · 5 items
[0]
Gender
[1]
[2]
[3]
[4]
[5] array · 6 items
[0]
Male/Female
[1]
197/101
[2]
0.917 (0.656–1.282)
[3]
0.611
[4]
[5]
[6] array · 5 items
[0]
Tumor stage
[1]
[2]
[3]
[4]
[7] array · 6 items
[0]
II/I
[1]
96/30
[2]
1.955 (0.759–5.034)
[3]
0.165
[4]
1.678 (0.649–4.338)
[5]
0.285
[8] array · 6 items
[0]
III/I
[1]
95/30
[2]
4.064 (1.623–10.176)
[3]
0.003
[4]
2.669 (1.030–6.920)
[5]
0.043
[9] array · 6 items
[0]
IV/I
[1]
77/30
[2]
9.737 (3.907–24.265)
[3]
<0.001
[4]
4.837 (1.755–13.328)
[5]
0.002
[10] array · 6 items
[0]
T
[1]
[2]
[3]
[4]
[5]
[11] array · 6 items
[0]
T3-4/T1-2
[1]
112/186
[2]
2.365 (1.719–3.255)
[3]
<0.001
[4]
[5]
[12] array · 6 items
[0]
N
[1]
[2]
[3]
[4]
[5]
[13] array · 6 items
[0]
N1-3/N0
[1]
260/38
[2]
2.847 (1.450–5.589)
[3]
0.002
[4]
[5]
[14] array · 6 items
[0]
M
[1]
[2]
[3]
[4]
[5]
[15] array · 6 items
[0]
M1/M0
[1]
27/271
[2]
3.806 (2.460–5.888)
[3]
<0.001
[4]
[5]
[16] array · 6 items
[0]
Number of lymph nodes examined
[1]
298
[2]
0.987 (0.976–0.998)
[3]
0.023
[4]
[5]
[17] array · 6 items
[0]
number of positive lymph nodes
[1]
298
[2]
1.072 (1.056–1.087)
[3]
<0.001
[4]
[5]
[18] array · 6 items
[0]
LNR
[1]
298
[2]
25.430 (13.312–48.578)
[3]
<0.001
[4]
7.030 (2.803–17.631)
[5]
<0.001
[19] array · 6 items
[0]
Risk score
[1]
298
[2]
5.205 (2.750–9.853)
[3]
<0.001
[4]
4.059 (2.097–7.855)
[5]
<0.001
locator
section[18]/table-wrap[2]#T2
gaps array · 2 items
[0]
asset:data:geo:GSE62254 not downloaded
[1]
asset:data:geo:GSE62254 licence not read
analysis object · 4 fields
state
complete
methods array · 6 items
[0] object · 10 fields
id
method-1
family
survival_analysis
specific
kaplan_meier
label
Survival analysis
dsl_operations array · 1 item
[0]
survival_km
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
1
band
verbatim
quote
All the survival analyses mentioned above were performed by Kaplan-Meier curve with a two-side log-rank test.
[1] object · 10 fields
id
method-2
family
survival_analysis
specific
cox_proportional_hazards
label
Survival analysis
dsl_operations array · 1 item
[0]
cox_ph
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.7
band
medium
quote
Cox regression
[2] object · 10 fields
id
method-3
family
survival_analysis
specific
log_rank_test
label
Survival analysis
dsl_operations array · 1 item
[0]
logrank_test
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.8
band
high
quote
log-rank
[3] object · 10 fields
id
method-4
family
network_analysis
specific
pathway_enrichment
label
Network / pathway analysis
dsl_operations array · 1 item
[0]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.7
band
medium
quote
pathway enrichment
[4] object · 10 fields
id
method-5
family
diagnostic_evaluation
specific
roc
label
Diagnostic test evaluation
dsl_operations array · 6 items
[0]
confusion_counts
[1]
roc_curve
[2]
sensitivity_specificity
[3]
solve_confusion_matrix
[4]
classification_metrics
[5]
published_precision_envelope
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
reference_standard_and_test
evidence object · 3 fields
score
0.7
band
medium
quote
ROC curve
[5] object · 10 fields
id
method-6
family
model_calibration
specific
decision_curve
label
Model calibration / clinical utility
dsl_operations array · 2 items
[0]
calibration_bins
[1]
net_benefit
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
predictions_and_outcomes
evidence object · 3 fields
score
0.7
band
medium
quote
decision curve analysis
targets array · 0 items
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 1 item
[0]
survival_km
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 1 item
[0]
GSE62254
resolved_accessions array · 1 item
[0]
GSE62254
statements array · 1 item
[0]
Publicly available datasets were analyzed in this study. This data can be found here: TCGA database: https://portal.gdc.cancer.gov/; GEO database: https://www.ncbi.nlm.nih.gov/geo/.
basis
The paper names GSE62254 in Gene Expression Omnibus (GEO2) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 1 item
[0]
survival_km
assets array · 4 items
[0]
source:pmid:34249086
[1]
data:geo:GSE62254
[2]
asset:table:pmid:34249086:1
[3]
asset:table:pmid:34249086:2
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE62254
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-10-31T18:32:13Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
34148
completion_tokens
3061
cached_tokens
11528
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
gaps array · 3 items
[0]
review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
mode
null
runs array · 0 items
gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:34249086
type
paper
label
pmid:34249086
[1] object · 3 fields
id
source:pmid:34249086
type
manuscript
label
PMID 34249086 full text
[2] object · 3 fields
id
data:geo:GSE62254
type
dataset
label
GEO GSE62254
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
[0] object · 3 fields
id
pmid:34249086
type
paper
label
pmid:34249086
[1] object · 3 fields
id
source:pmid:34249086
type
manuscript
label
PMID 34249086 full text
[2] object · 3 fields
id
data:geo:GSE62254
type
dataset
label
GEO GSE62254
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-34249086
type
extraction
used array · 1 item
[0]
source:pmid:34249086
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE62254
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE62254
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
label
Corpus assay engine
[1] object · 3 fields
id
agent:minimax-reader
type
software
label
MiniMax literature reader
source_run_id
reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
snapshot_id
ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:34249086
parent_hash
sha256:26f3f269023e122a75138150d0394e479120e57df0b69a9f83e16fc409a95138
fork_of
null
gaps array · 6 items
[0]
asset:data:geo:GSE62254 licence not read
[1]
asset:data:geo:GSE62254 not downloaded
[2]
execution.not_run
[3]
review.human_critique
[4]
review.independent_reader
[5]
review.machine_critique
assays array · 3 items
[0] object · 11 fields
role
data_generation
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.93
evidence array · 1 item
[0]
s used for external validation. Quantitative real-time PCR (qRT-PCR) was used to detected the mRNA expr
order_basis
paper_text_order:1177
id
assay:1
[1] object · 11 fields
role
data_generation
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cell_culture
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.77
evidence array · 1 item
[0]
ine SNU-5 was obtained from ATCC. Cells were cultured in RPMI-1640 medium (Gibco, Grand Island, NY, U
order_basis
paper_text_order:2959
id
assay:2
[2] object · 11 fields
role
analysis
definition_id
survival_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
survival_km
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
All the survival analyses mentioned above were performed by Kaplan-Meier curve with a two-side log-rank test.
order_basis
consumes_earlier_output
id
assay:3
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34249086", "kind": "science-record", "revision": 8, "content_hash": "sha256:8a64fa13c57dc8b290fdb2185dccd3c336cc51c8674bbded66e64b74593a43ff", "created_at": "2026-11-01T15:41:42Z", "updated_at": "2026-11-01T22:47:03Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of an EMT-Related Gene Signature for Predicting Overall Survival in Gastric Cancer.", "doi": "10.3389/fgene.2021.661306", "pmid": "34249086", "authors": ["Weiyu Dai", "Yizhi Xiao", "Weimei Tang", "Jiaying Li", "Linjie Hong", "Jieming Zhang", "Miaomiao Pei", "Jianjiao Lin", "Side Liu", "Xiaosheng Wu", "Li Xiang", "Jide Wang"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "BACKGROUND: It has been widely reported that epithelial-mesenchymal transition (EMT) is associated with malignant progression in gastric cancer (GC). Integration of the molecules related to EMT for predicting overall survival (OS) is meaningful for understanding the role of EMT in GC. Here, we aimed to establish an EMT-related gene signature in GC.\nMETHODS: Transcriptional profiles and clinical data of GC were downloaded from The Cancer Genome Atlas (TCGA). We constructed EMT-related gene signature for predicting OS by using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. Time-dependent receiver operating characteristic (ROC), Kaplan-Meier analysis were performed to assess its predictive value. A nomogram combining the prognostic signature with clinical characteristics for OS prediction was established. And its predictive power was estimated by concordance index (C-index), time-dependent ROC curve, calibration curve and decision curve analysis (DCA). GSE62254 dataset from Gene Expression Omnibus (GEO) was used for external validation. Quantitative real-time PCR (qRT-PCR) was used to detected the mRNA expression of the five EMT-related genes in human normal gastric mucosal and GC cell lines. To further understand the potential mechanisms of the signature, Gene Set Enrichment Analysis (GSEA), pathway enrichment analysis, predictions of transcription factors (TFs)/miRNAs were performed.\nRESULTS: A novel EMT-related gene signature (including ITGAV, DAB2, SERPINE1, MATN3, PLOD2) was constructed for OS prediction of GC. With external validation, ROC curves indicated the signature's good performance. Patients stratified into high- and low-risk groups based on the signature yielded significantly different prognosis. Univariate and multivariate Cox regression suggested that the signature was an independent prognostic variable. Nomogram for prognostication including the signature presented better predictive accuracy and clinical usefulness than the similar model without risk score to some extent with external validation. The qRT-PCR assays suggested that high expression of the five EMT-related genes could be found in human GC cell lines compared with normal gastric mucosal cell line. GSEA and pathway enrichment analysis revealed that focal adhesion and ECM-receptor interaction might be the two important pathways to the signature.\nCONCLUSION: Our EMT-related gene signature may have practical application as an independent prognostic factor in GC.", "claims": [{"id": "claim-method", "statement": "All the survival analyses mentioned above were performed by Kaplan-Meier curve with a two-side log-rank test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34249086", "locator": "sections[13] \"Survival Analysis\" paragraph 2", "quote": "All the survival analyses mentioned above were performed by Kaplan-Meier curve with a two-side log-rank test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA database: https://portal.gdc.cancer.gov/; GEO database: https://www.ncbi.nlm.nih.gov/geo/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34249086", "locator": "sections[24] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA database: https://portal.gdc.cancer.gov/; GEO database: https://www.ncbi.nlm.nih.gov/geo/."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34249086"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE62254"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE62254"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34249086", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2021.661306", "sha256": "sha256:3536d4abb8b0006693c556c07488c620c622e4dbee7c4de98deed3e5e5233c94", "bytes": 45307, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2021.661306", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8264558", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE62254", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62254", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE62254", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA database: https://portal.gdc.cancer.gov/; GEO database: https://www.ncbi.nlm.nih.gov/geo/.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA database: https://portal.gdc.cancer.gov/; GEO database: https://www.ncbi.nlm.nih.gov/geo/.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1523727", "GSM1523728", "GSM1523729", "GSM1523744", "GSM1523745", "GSM1523746", "GSM1523747", "GSM1523748", "GSM1523765", "GSM1523768", "GSM1523769", "GSM1523770", "GSM1523771", "GSM1523772", "GSM1523773", "GSM1523774", "GSM1523775", "GSM1523776", "GSM1523777", "GSM1523778", "GSM1523779", "GSM1523780", "GSM1523781", "GSM1523782", "GSM1523783", "GSM1523784", "GSM1523785", "GSM1523786", "GSM1523787", "GSM1523788", "GSM1523789", "GSM1523790", "GSM1523791", "GSM1523792", "GSM1523793", "GSM1523794", "GSM1523795", "GSM1523796", "GSM1523797", "GSM1523798", "GSM1523799", "GSM1523800", "GSM1523801", "GSM1523802", "GSM1523803", "GSM1523804", "GSM1523805", "GSM1523806", "GSM1523807", "GSM1523808", "GSM1523809", "GSM1523810", "GSM1523811", "GSM1523812", "GSM1523813", "GSM1523814", 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