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pmid:36879671

Integrated bioinformatics analyses identifying key transcriptomes correlated with prognosis and immune infiltrations in lung squamous cell carcinoma.

Rana A Alghamdi · Maryam H Al-Zahrani

Saudi journal of biological sciences · 2023 doi:10.1016/j.sjbs.2023.103596

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Experiment

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Integrated bioinformatics analyses identifying key transcriptomes correlated with prognosis and immune infiltrations in lung squamous cell carcinoma.
doi
10.1016/j.sjbs.2023.103596
pmid
36879671
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Rana A Alghamdi
[1]
Maryam H Al-Zahrani
journal
Saudi journal of biological sciences
year
2023
abstract
Background: Lung Squamous Cell Carcinoma (LUSC) is a major subtype of lung malignancies and is associated with the cause of cancer-mediated mortality worldwide. However, identification of transcriptomic signatures associated with survival-prognosis and immunity of tumor remains lacking. Method: The GSE2088, GSE6044, GSE19188, GSE21933, GSE33479, GSE33532, and GSE74706 were integrated for identifying differentially expressed genes (DEGs) with combined effect sizes. Also, the TCGA LUSC cohort was used for further analysis. A series of bioinformatics methods were utilized for conducting the whole study. Results: The 831 genes (such as DSG3, PKP1, DSC3, TPX2, and UBE2C) were found upregulated and the 731 genes (such as ABCA8, SELENBP1, FAM107A, and CACNA2D2) were downregulated in the LUSC. The functional enrichment analysis identifies the upregulated KEGG pathways, including cell cycle, DNA replication, base excision repair, proteasome, mismatch repair, and cellular senescence. Also, the key hub genes (such as EGFR, HRAS, JUN, CDH1, BRCA1, CASP3, RHOA, HDAC1, HIF1A, and CCNA2) were identified along with the eight gene modules that were significantly related to the protein-protein interaction (PPI). The clinical analyses identified that the overexpression group of CDH3, PLAU, PKP3, STIL, CALU, LOXL2, POSTN, DPP3, GALNT2, LOX, and ITPA are substantially associated with a poor survival prognosis and the downregulated group of IL18R1 showed a similar trend. Moreover, our investigation demonstrated that the survival-associated genes were correlated with the stromal and immune scores in LUSC, indicating that the survival-associated genes regulate tumor immunity. The survival-associated genes were genetically altered in 27% of LUSC patients and showed excellent diagnostic efficiency. Finally, the consistent expression level of CDH3, PLAU, PKP3, STIL, CALU, LOXL2, POSTN, DPP3, GALNT2, and ITPA were found in the TCGA LUSC cohort. Conclusions: The identification of key transcriptomic signatures can be elucidated by the crucial mechanism of LUSC carcinogenesis.
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The differential expression analysis was conducted using the NetworkAnalyst (Xia et al., 2015) software, an online-based tool.
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sections[4] "Exploration of differentially expressed genes (DEGs) in LUSC" paragraph 2
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The differential expression analysis was conducted using the NetworkAnalyst (Xia et al., 2015) software, an online-based tool.
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The 831 genes (such as DSG3, PKP1, DSC3, TPX2, and UBE2C) were found upregulated and the 731 genes (such as ABCA8, SELENBP1, FAM107A, and CACNA2D2) were downregulated in the LUSC.
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The 831 genes (such as DSG3, PKP1, DSC3, TPX2, and UBE2C) were found upregulated and the 731 genes (such as ABCA8, SELENBP1, FAM107A, and CACNA2D2) were downregulated in the LUSC.
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The 831 genes (such as DSG3, PKP1, DSC3, TPX2, and UBE2C) were found upregulated and the 731 genes (such as ABCA8, SELENBP1, FAM107A, and CACNA2D2) were downregulated in the LUSC.
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GSM828350
sample_count
122
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null
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null
platform
6480
taxon
Homo sapiens
title
Molecular characterisation of the multistep process of lung squamous carcinogenesis by gene expression profiling
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
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[5] object · 15 fields
id
data:geo:GSE33532
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application/vnd.ncbi.geo-series+json
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE33532
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1GSE2088GPL962Subclassification of lung squamous cell carcinoma3048(Fujiwara et al., 2012)
structure object · 15 fields
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GEO accession URL
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1GSE2088GPL962Subclassification of lung squamous cell carcinoma3048(Fujiwara et al., 2012)
access_statement_kind
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[98]
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[99]
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100
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null
group_sizes_basis
null
platform
570
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Homo sapiens
title
Intratumor heterogeneity of gene expression profiles in early stage non-small cell lung cancer (NSCLC)
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[6] object · 15 fields
id
data:geo:GSE6044
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geo-series
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application/vnd.ncbi.geo-series+json
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6044
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GSE6044
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null
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1GSE2088GPL962Subclassification of lung squamous cell carcinoma3048(Fujiwara et al., 2012)
structure object · 15 fields
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GEO
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GEO accession URL
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1GSE2088GPL962Subclassification of lung squamous cell carcinoma3048(Fujiwara et al., 2012)
access_statement_kind
repository_route_statement
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GSM140166
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GSM140220
[46]
GSM140221
sample_count
47
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null
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null
platform
201
taxon
Homo sapiens
title
Genetic programming and gene expression profiling for molecular discrimination and characterization of lung cancers
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
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[7] object · 15 fields
id
data:geo:GSE74706
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geo-series
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application/vnd.ncbi.geo-series+json
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE74706
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null
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null
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null
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1GSE2088GPL962Subclassification of lung squamous cell carcinoma3048(Fujiwara et al., 2012)
structure object · 15 fields
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GEO
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GEO accession URL
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1GSE2088GPL962Subclassification of lung squamous cell carcinoma3048(Fujiwara et al., 2012)
access_statement_kind
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GSM1930616
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[35]
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sample_count
36
group_sizes
null
group_sizes_basis
null
platform
13497
taxon
Homo sapiens
title
Transcriptome of human NSCLC tissues
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 14 items
[0]
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[1]
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[2]
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[3]
asset:data:geo:GSE2088 licence not read
[4]
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[5]
asset:data:geo:GSE21933 licence not read
[6]
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[7]
asset:data:geo:GSE33479 licence not read
[8]
asset:data:geo:GSE33532 not downloaded
[9]
asset:data:geo:GSE33532 licence not read
[10]
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[11]
asset:data:geo:GSE6044 licence not read
[12]
asset:data:geo:GSE74706 not downloaded
[13]
asset:data:geo:GSE74706 licence not read
analysis object · 4 fields
state
partial
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[0] object · 10 fields
id
method-1
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survival_analysis
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kaplan_meier
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Survival analysis
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[0]
survival_km
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parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
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0.8
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Kaplan-Meier
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method-2
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survival_analysis
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Survival analysis
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[0]
logrank_test
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parameters object · 0 fields
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[0]
time_to_event_with_censoring
evidence object · 3 fields
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0.8
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method-3
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network_analysis
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Network / pathway analysis
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edge_list
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0.7
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protein-protein interaction
[3] object · 10 fields
id
method-4
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null
specific
null
label
NetworkAnalyst software with combined effect sizes
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missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 0 items
evidence object · 3 fields
score
1
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verbatim
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The differential expression analysis was conducted using the NetworkAnalyst (Xia et al., 2015) software, an online-based tool.
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gaps array · 1 item
[0]
method.reader_named_unmapped
capability object · 3 fields
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complete
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[0] object · 6 fields
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capability:computational_analysis
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[0]
meta_analysis
[1]
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[7]
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[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
state
complete
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R1
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nothing:replicable_now
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method object · 5 fields
tier
R1
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true
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survival_km
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The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier.
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tier
R1
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capability:computational_analysis
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owned
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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
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GSE2088
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[2]
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[3]
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GSE33479
[5]
GSE33532
[6]
GSE74706
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[0]
GSE2088
[1]
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[2]
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[3]
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[4]
GSE33479
[5]
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[6]
GSE74706
statements array · 1 item
[0]
1GSE2088GPL962Subclassification of lung squamous cell carcinoma3048(Fujiwara et al., 2012)
basis
The paper names GSE2088, GSE6044, GSE19188, GSE21933, GSE33479, GSE33532, GSE74706 in NCBI 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 · 1 item
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survival_km
assets array · 2 items
[0]
source:pmid:36879671
[1]
data:geo:GSE19188
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[0]
run_analysis
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readers array · 0 items
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[0]
data:geo:GSE19188
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review object · 5 fields
state
partial
machine_critique object · 5 fields
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extraction_review
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MiniMax-M3.1-Flash
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minimax
provider_family
minimax
read_at
2026-11-01T18:32:47Z
independence
single_reader
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method
verbatim
availability
null
calls
5
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14648
completion_tokens
2365
cached_tokens
256
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[0] object · 4 fields
id
extraction
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complete
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MiniMax-M3.1-Flash
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minimax
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[1]
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execution object · 5 fields
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absent
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not_run
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null
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execution.not_run
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pmid:36879671
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paper
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pmid:36879671
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source:pmid:36879671
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manuscript
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PMID 36879671 full text
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data:geo:GSE19188
type
dataset
label
GEO GSE19188
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[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
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pmid:36879671
type
paper
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pmid:36879671
[1] object · 3 fields
id
source:pmid:36879671
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manuscript
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PMID 36879671 full text
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id
data:geo:GSE19188
type
dataset
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GEO GSE19188
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agent:corpus-assay-engine
[1] object · 4 fields
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activity-read-36879671
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extraction
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[0]
source:pmid:36879671
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agent:minimax-reader
[2] object · 4 fields
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activity-resolve-GSE19188
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[0]
data:geo:GSE19188
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agent:corpus-assay-engine
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agent:corpus-assay-engine
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agent:minimax-reader
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dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
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lineage object · 4 fields
parent_id
pmid:36879671
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sha256:fa5db96045687a26a8bc7b7a3f19eb1de52dd5c43c8abbb879522a94a7b68be0
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null
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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[11]
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[12]
asset:data:geo:GSE74706 licence not read
[13]
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[14]
execution.not_run
[15]
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[16]
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[17]
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[0] object · 11 fields
role
analysis
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survival_analysis
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f2132e96ae6c7a4e
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survival_km
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supported
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dsl_catalogue
f2132e96ae6c7a4e
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36879671", "kind": "science-record", "revision": 3, "content_hash": "sha256:dbadf7d80c5ada3b3bfbd808d41af38e851edf512e12d145a1326186afa044ea", "created_at": "2026-11-01T19:01:31Z", "updated_at": "2026-11-01T22:09:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrated bioinformatics analyses identifying key transcriptomes correlated with prognosis and immune infiltrations in lung squamous cell carcinoma.", "doi": "10.1016/j.sjbs.2023.103596", "pmid": "36879671", "authors": ["Rana A Alghamdi", "Maryam H Al-Zahrani"], "journal": "Saudi journal of biological sciences", "year": 2023, "abstract": "Background: Lung Squamous Cell Carcinoma (LUSC) is a major subtype of lung malignancies and is associated with the cause of cancer-mediated mortality worldwide. However, identification of transcriptomic signatures associated with survival-prognosis and immunity of tumor remains lacking.\nMethod: The GSE2088, GSE6044, GSE19188, GSE21933, GSE33479, GSE33532, and GSE74706 were integrated for identifying differentially expressed genes (DEGs) with combined effect sizes. Also, the TCGA LUSC cohort was used for further analysis. A series of bioinformatics methods were utilized for conducting the whole study.\nResults: The 831 genes (such as DSG3, PKP1, DSC3, TPX2, and UBE2C) were found upregulated and the 731 genes (such as ABCA8, SELENBP1, FAM107A, and CACNA2D2) were downregulated in the LUSC. The functional enrichment analysis identifies the upregulated KEGG pathways, including cell cycle, DNA replication, base excision repair, proteasome, mismatch repair, and cellular senescence. Also, the key hub genes (such as EGFR, HRAS, JUN, CDH1, BRCA1, CASP3, RHOA, HDAC1, HIF1A, and CCNA2) were identified along with the eight gene modules that were significantly related to the protein-protein interaction (PPI). The clinical analyses identified that the overexpression group of CDH3, PLAU, PKP3, STIL, CALU, LOXL2, POSTN, DPP3, GALNT2, LOX, and ITPA are substantially associated with a poor survival prognosis and the downregulated group of IL18R1 showed a similar trend. Moreover, our investigation demonstrated that the survival-associated genes were correlated with the stromal and immune scores in LUSC, indicating that the survival-associated genes regulate tumor immunity. The survival-associated genes were genetically altered in 27% of LUSC patients and showed excellent diagnostic efficiency. Finally, the consistent expression level of CDH3, PLAU, PKP3, STIL, CALU, LOXL2, POSTN, DPP3, GALNT2, and ITPA were found in the TCGA LUSC cohort.\nConclusions: The identification of key transcriptomic signatures can be elucidated by the crucial mechanism of LUSC carcinogenesis.", "claims": [{"id": "claim-method", "statement": "The differential expression analysis was conducted using the NetworkAnalyst (Xia et al., 2015) software, an online-based tool.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36879671", "locator": "sections[4] \"Exploration of differentially expressed genes (DEGs) in LUSC\" paragraph 2", "quote": "The differential expression analysis was conducted using the NetworkAnalyst (Xia et al., 2015) software, an online-based tool."}], "state": "complete"}, {"id": "claim-data-access", "statement": "1GSE2088GPL962Subclassification of lung squamous cell carcinoma3048(Fujiwara et al., 2012)", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36879671", "locator": "sections[3] \"Datasets collection and preprocessing\" paragraph 3", "quote": "1GSE2088GPL962Subclassification of lung squamous cell carcinoma3048(Fujiwara et al., 2012)"}], "state": "complete"}, {"id": "claim-target-result", "statement": "The 831 genes (such as DSG3, PKP1, DSC3, TPX2, and UBE2C) were found upregulated and the 731 genes (such as ABCA8, SELENBP1, FAM107A, and CACNA2D2) were downregulated in the LUSC.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36879671", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The 831 genes (such as DSG3, PKP1, DSC3, TPX2, and UBE2C) were found upregulated and the 731 genes (such as ABCA8, SELENBP1, FAM107A, and CACNA2D2) were downregulated in the LUSC."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The 831 genes (such as DSG3, PKP1, DSC3, TPX2, and UBE2C) were found upregulated and the 731 genes (such as ABCA8, SELENBP1, FAM107A, and CACNA2D2) were downregulated in the LUSC.", "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:36879671"], "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:GSE19188"], "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:GSE19188"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36879671", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.sjbs.2023.103596", "sha256": 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