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pmid:34384424

Identification of latent biomarkers in connection with progression and prognosis in oral cancer by comprehensive bioinformatics analysis.

Abdusemer Reyimu · Ying Chen · Xudong Song · Wubi Zhou · Jingjing Dai · Feng Jiang

World journal of surgical oncology · 2021 doi:10.1186/s12957-021-02360-w

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Experiment

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title
Identification of latent biomarkers in connection with progression and prognosis in oral cancer by comprehensive bioinformatics analysis.
doi
10.1186/s12957-021-02360-w
pmid
34384424
authors array · 6 items
[0]
Abdusemer Reyimu
[1]
Ying Chen
[2]
Xudong Song
[3]
Wubi Zhou
[4]
Jingjing Dai
[5]
Feng Jiang
journal
World journal of surgical oncology
year
2021
abstract
BACKGROUND: Oral cancer (OC) is a common and dangerous malignant tumor with a low survival rate. However, the micro level mechanism has not been explained in detail. METHODS: Gene and miRNA expression micro array data were extracted from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) and miRNAs (DE miRNAs) were identified by R software. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of genes and genomes (KEGG) pathway analysis were used to assess the potential molecular mechanisms of DEGs. Cytoscape software was utilized to construct protein-protein interaction (PPI) network and miRNA-gene network. Central genes were screened out with the participation of gene degree, molecular complex detection (MCODE) plugin, and miRNA-gene network. Then, the identified genes were checked by The Cancer Genome Atlas (TCGA) gene expression profile, Kaplan-Meier data, Oncomine, and the Human Protein Atlas database. Receiver operating characteristic (ROC) curve was drawn to predict the diagnostic efficiency of crucial gene level in normal and tumor tissues. Univariate and multivariate Cox regression were used to analyze the effect of dominant genes and clinical characteristics on the overall survival rate of OC patients. RESULTS: Gene expression data of gene expression profiling chip(GSE9844, GSE30784, and GSE74530) were obtained from GEO database, including 199 tumor and 63 non-tumor samples. We identified 298 gene mutations, including 200 upregulated and 98 downregulated genes. GO functional annotation analysis showed that DEGs were enriched in extracellular structure and extracellular matrix containing collagen. In addition, KEGG pathway enrichment analysis demonstrated that the DEGs were significantly enriched in IL-17 signaling pathway and PI3K-Akt signaling pathway. Then, we detected three most relevant modules in PPI network. Central genes (CXCL8, DDX60, EIF2AK2, GBP1, IFI44, IFI44L, IFIT1, IL6, MMP9,CXCL1, CCL20, RSAD2, and RTP4) were screened out with the participation of MCODE plugin, gene degree, and miRNA-gene network. TCGA gene expression profile and Kaplan-Meier analysis showed that high expression of CXCL8, DDX60, IL6, and RTP4 was associated with poor prognosis in OC patients, while patients with high expression of IFI44L and RSAD2 had a better prognosis. The elevated expression of CXCL8, DDX60, IFI44L, RSAD2, and RTP44 in OC was verified by using Oncomine database. ROC curve showed that the mRNA levels of these five genes had a helpful diagnostic effect on tumor tissue. The Human Protein Atlas database showed that the protein expressions of DDX60, IFI44L, RSAD2, and RTP44 in tumor tissues were higher than those in normal tissues. Finally, univariate and multivariate Cox regression showed that DDX60, IFI44L, RSAD2, and RTP44 were independent prognostic indicators of OC. CONCLUSION: This study revealed the potential biomarkers and relevant pathways of OC from publicly available GEO database, and provided a theoretical basis for elucidating the diagnosis, treatment, and prognosis of OC.
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The R package of “limma” was used for analysis, and screening conditions were adjusted P < 0.05, |log2FC| > 1.
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Univariate and multivariate analyses of the correlation of CXCL8, DDX60, IFI44L, RSAD2, and RTP4 expression with overall survival (OS) among OC patients
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0.047
[4]
0.393
[5]
0.990–1.021
[6]
0.000
[7] array · 7 items
[0]
IFI44L
[1]
1.419
[2]
1.001–2.012
[3]
0.049
[4]
1.739
[5]
0.885–1.134
[6]
0.029
[8] array · 7 items
[0]
RSAD2
[1]
1.689
[2]
1.133–2.512
[3]
0.010
[4]
1.853
[5]
0.990–1.014
[6]
0.017
[9] array · 7 items
[0]
RTP4
[1]
0.526
[2]
0.318–0.871
[3]
0.013
[4]
0.351
[5]
0.956–0.998
[6]
0.000
locator
section[14]/table-wrap[1]#Tab1
gaps array · 8 items
[0]
asset:data:geo:GSE124566 not downloaded
[1]
asset:data:geo:GSE124566 licence not read
[2]
asset:data:geo:GSE30784 not downloaded
[3]
asset:data:geo:GSE30784 licence not read
[4]
asset:data:geo:GSE74530 not downloaded
[5]
asset:data:geo:GSE74530 licence not read
[6]
asset:data:geo:GSE9844 not downloaded
[7]
asset:data:geo:GSE9844 licence not read
analysis object · 4 fields
state
partial
methods array · 6 items
[0] object · 10 fields
id
method-1
family
differential_expression
specific
limma_voom
label
Differential expression analysis
dsl_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
score
1
band
verbatim
quote
The R package of “limma” was used for analysis, and screening conditions were adjusted P < 0.05, |log2FC| > 1.
[1] object · 10 fields
id
method-2
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
0.7
band
medium
quote
Kaplan-Meier
[2] object · 10 fields
id
method-3
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
[3] object · 10 fields
id
method-4
family
network_analysis
specific
ppi_network
label
Network / pathway analysis
dsl_operations array · 3 items
[0]
build_graph
[1]
centrality_scores
[2]
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
protein-protein interaction
[4] object · 10 fields
id
method-5
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
[5] object · 10 fields
id
method-6
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
targets array · 0 items
gaps array · 1 item
[0]
method.reader_differs_from_extractor
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 · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
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: limma_voom.
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 · 4 items
[0]
GSE9844
[1]
GSE30784
[2]
GSE74530
[3]
GSE124566
resolved_accessions array · 4 items
[0]
GSE9844
[1]
GSE30784
[2]
GSE74530
[3]
GSE124566
statements array · 1 item
[0]
The datasets supporting the conclusion of this article are included within the article.
basis
The paper names GSE9844, GSE30784, GSE74530, GSE124566 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
assets array · 3 items
[0]
source:pmid:34384424
[1]
data:geo:GSE124566
[2]
asset:table:pmid:34384424:1
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:GSE124566
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
2026-10-31T18:33:32Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
22301
completion_tokens
1301
cached_tokens
776
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:34384424
type
paper
label
pmid:34384424
[1] object · 3 fields
id
source:pmid:34384424
type
manuscript
label
PMID 34384424 full text
[2] object · 3 fields
id
data:geo:GSE124566
type
dataset
label
GEO GSE124566
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:34384424
type
paper
label
pmid:34384424
[1] object · 3 fields
id
source:pmid:34384424
type
manuscript
label
PMID 34384424 full text
[2] object · 3 fields
id
data:geo:GSE124566
type
dataset
label
GEO GSE124566
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-34384424
type
extraction
used array · 1 item
[0]
source:pmid:34384424
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE124566
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE124566
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:34384424
parent_hash
sha256:38e6b77567ca37f2cf894bee7cbf7b964b38b7b95396b4c7f926aa427b5d5e0b
fork_of
null
gaps array · 13 items
[0]
asset:data:geo:GSE124566 licence not read
[1]
asset:data:geo:GSE124566 not downloaded
[2]
asset:data:geo:GSE30784 licence not read
[3]
asset:data:geo:GSE30784 not downloaded
[4]
asset:data:geo:GSE74530 licence not read
[5]
asset:data:geo:GSE74530 not downloaded
[6]
asset:data:geo:GSE9844 licence not read
[7]
asset:data:geo:GSE9844 not downloaded
[8]
execution.not_run
[9]
method.reader_differs_from_extractor
[10]
review.human_critique
[11]
review.independent_reader
[12]
review.machine_critique
assays array · 1 item
[0] object · 11 fields
role
analysis
definition_id
differential_expression
definition_version
f2132e96ae6c7a4e
required_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
The R package of “limma” was used for analysis, and screening conditions were adjusted P < 0.05, |log2FC| > 1.
order_basis
analysis_only
id
assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34384424", "kind": "science-record", "revision": 8, "content_hash": "sha256:c14e0337cc78f0c8c076ad1e1e84a9050d923ea050790acfb7da8a74900b3210", "created_at": "2026-11-01T15:41:47Z", "updated_at": "2026-11-01T22:47:18Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of latent biomarkers in connection with progression and prognosis in oral cancer by comprehensive bioinformatics analysis.", "doi": "10.1186/s12957-021-02360-w", "pmid": "34384424", "authors": ["Abdusemer Reyimu", "Ying Chen", "Xudong Song", "Wubi Zhou", "Jingjing Dai", "Feng Jiang"], "journal": "World journal of surgical oncology", "year": 2021, "abstract": "BACKGROUND: Oral cancer (OC) is a common and dangerous malignant tumor with a low survival rate. However, the micro level mechanism has not been explained in detail.\nMETHODS: Gene and miRNA expression micro array data were extracted from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) and miRNAs (DE miRNAs) were identified by R software. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of genes and genomes (KEGG) pathway analysis were used to assess the potential molecular mechanisms of DEGs. Cytoscape software was utilized to construct protein-protein interaction (PPI) network and miRNA-gene network. Central genes were screened out with the participation of gene degree, molecular complex detection (MCODE) plugin, and miRNA-gene network. Then, the identified genes were checked by The Cancer Genome Atlas (TCGA) gene expression profile, Kaplan-Meier data, Oncomine, and the Human Protein Atlas database. Receiver operating characteristic (ROC) curve was drawn to predict the diagnostic efficiency of crucial gene level in normal and tumor tissues. Univariate and multivariate Cox regression were used to analyze the effect of dominant genes and clinical characteristics on the overall survival rate of OC patients.\nRESULTS: Gene expression data of gene expression profiling chip(GSE9844, GSE30784, and GSE74530) were obtained from GEO database, including 199 tumor and 63 non-tumor samples. We identified 298 gene mutations, including 200 upregulated and 98 downregulated genes. GO functional annotation analysis showed that DEGs were enriched in extracellular structure and extracellular matrix containing collagen. In addition, KEGG pathway enrichment analysis demonstrated that the DEGs were significantly enriched in IL-17 signaling pathway and PI3K-Akt signaling pathway. Then, we detected three most relevant modules in PPI network. Central genes (CXCL8, DDX60, EIF2AK2, GBP1, IFI44, IFI44L, IFIT1, IL6, MMP9,CXCL1, CCL20, RSAD2, and RTP4) were screened out with the participation of MCODE plugin, gene degree, and miRNA-gene network. TCGA gene expression profile and Kaplan-Meier analysis showed that high expression of CXCL8, DDX60, IL6, and RTP4 was associated with poor prognosis in OC patients, while patients with high expression of IFI44L and RSAD2 had a better prognosis. The elevated expression of CXCL8, DDX60, IFI44L, RSAD2, and RTP44 in OC was verified by using Oncomine database. ROC curve showed that the mRNA levels of these five genes had a helpful diagnostic effect on tumor tissue. The Human Protein Atlas database showed that the protein expressions of DDX60, IFI44L, RSAD2, and RTP44 in tumor tissues were higher than those in normal tissues. Finally, univariate and multivariate Cox regression showed that DDX60, IFI44L, RSAD2, and RTP44 were independent prognostic indicators of OC.\nCONCLUSION: This study revealed the potential biomarkers and relevant pathways of OC from publicly available GEO database, and provided a theoretical basis for elucidating the diagnosis, treatment, and prognosis of OC.", "claims": [{"id": "claim-method", "statement": "The R package of “limma” was used for analysis, and screening conditions were adjusted P < 0.05, |log2FC| > 1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34384424", "locator": "sections[10] \"Identification of DEGs in OC\" paragraph 2", "quote": "The R package of “limma” was used for analysis, and screening conditions were adjusted P < 0.05, |log2FC| > 1."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets supporting the conclusion of this article are included within the article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34384424", "locator": "sections[22] \"notes\" paragraph 1", "quote": "The datasets supporting the conclusion of this article are included within the article."}], "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:34384424"], "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:GSE124566"], "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:GSE124566"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34384424", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12957-021-02360-w", "sha256": "sha256:f551616dc35b4d5133768191045c941614074a72a4f6b39b213184d1b751c596", "bytes": 28755, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12957-021-02360-w", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8361649", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE124566", "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=GSE124566", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE124566", "version": null, "note": "The datasets supporting the conclusion of this article are included within the article.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets supporting the conclusion of this article are included within the article.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3536880", "GSM3536881", "GSM3536882", "GSM3536883", "GSM3536884", "GSM3536885", "GSM3536886", "GSM3536887", "GSM3536888", "GSM3536889", "GSM3536890", "GSM3536891", "GSM3536892", "GSM3536893", "GSM3536894", "GSM3536895", "GSM3536896", "GSM3536897", "GSM3536898", "GSM3536899"], "sample_count": 20, "group_sizes": null, "group_sizes_basis": null, "platform": "18402", "taxon": "Homo sapiens", "title": "MicroRNA-204-5p is a tumor suppressor and potential therapeutic target in head and neck squamous cell carcinoma", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE30784", "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=GSE30784", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE30784", "version": null, "note": "The datasets supporting the conclusion of this article are included within the article.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets supporting the conclusion of this article are included within the article.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM764749", "GSM764750", "GSM764751", "GSM764752", "GSM764753", "GSM764754", "GSM764755", "GSM764756", "GSM764757", "GSM764758", "GSM764759", "GSM764760", "GSM764761", "GSM764762", "GSM764763", "GSM764764", "GSM764765", "GSM764766", "GSM764767", "GSM764768", "GSM764769", "GSM764770", "GSM764771", "GSM764772", "GSM764773", "GSM764774", "GSM764775", "GSM764776", "GSM764777", "GSM764778", "GSM764779", "GSM764780", "GSM764781", "GSM764782", "GSM764783", "GSM764784", "GSM764785", "GSM764786", "GSM764787", "GSM764788", "GSM764789", "GSM764790", "GSM764791", "GSM764792", "GSM764793", "GSM764794", "GSM764795", "GSM764796", "GSM764797", "GSM764798", "GSM764799", "GSM764800", "GSM764801", "GSM764802", "GSM764803", "GSM764804", "GSM764805", "GSM764806", "GSM764807", "GSM764808", "GSM764809", "GSM764810", "GSM764811", "GSM764812", "GSM764813", "GSM764814", "GSM764815", "GSM764816", "GSM764817", "GSM764818", "GSM764819", "GSM764820", "GSM764821", "GSM764822", "GSM764823", "GSM764824", "GSM764825", "GSM764826", "GSM764827", "GSM764828", "GSM764829", "GSM764830", "GSM764831", "GSM764832", "GSM764833", "GSM764834", "GSM764835", "GSM764836", "GSM764837", "GSM764838", "GSM764839", "GSM764840", "GSM764841", "GSM764842", "GSM764843", "GSM764844", "GSM764845", "GSM764846", "GSM764847", "GSM764848", "GSM764849", 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