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pmid:36506325

Construction of the model for predicting prognosis by key genes regulating EGFR-TKI resistance.

Jinke Zhuge · Xiuqing Wang · Jingtai Li · Tongyuan Wang · Hongkang Wang · Mingxing Yang · Wen Dong · Yong Gao

Frontiers in genetics · 2022 doi:10.3389/fgene.2022.968376

Paper

complete

Experiment

partial

Data

partial

Analysis

partial

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title
Construction of the model for predicting prognosis by key genes regulating EGFR-TKI resistance.
doi
10.3389/fgene.2022.968376
pmid
36506325
authors array · 8 items
[0]
Jinke Zhuge
[1]
Xiuqing Wang
[2]
Jingtai Li
[3]
Tongyuan Wang
[4]
Hongkang Wang
[5]
Mingxing Yang
[6]
Wen Dong
[7]
Yong Gao
journal
Frontiers in genetics
year
2022
abstract
Background: Previous studies have suggested that patients with lung adenocarcinoma (LUAD) will significantly benefit from epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). However, many LUAD patients will develop resistance to EGFR-TKI. Thus, our study aims to develop models to predict EGFR-TKI resistance and the LUAD prognosis. Methods: Two Gene Expression Omnibus (GEO) datasets (GSE31625 and GSE34228) were used as the discovery datasets to find the common differentially expressed genes (DEGs) in EGFR-TKI resistant LUAD profiles. The association of these common DEGs with LUAD prognosis was investigated in The Cancer Genome Atlas (TCGA) database. Moreover, we constructed the risk score for prognosis prediction of LUAD by LASSO analysis. The performance of the risk score for predicting LUAD prognosis was calculated using an independent dataset (GSE37745). A random forest model by risk score genes was trained in the training dataset, and the diagnostic ability for distinguishing sensitive and EGFR-TKI resistant samples was validated in the internal testing dataset and external testing datasets (GSE122005, GSE80344, and GSE123066). Results: From the discovery datasets, 267 common upregulated genes and 374 common downregulated genes were identified. Among these common DEGs, there were 59 genes negatively associated with prognosis, while 21 genes exhibited positive correlations with prognosis. Eight genes (ABCC2, ARL2BP, DKK1, FUT1, LRFN4, PYGL, SMNDC1, and SNAI2) were selected to construct the risk score signature. In both the discovery and independent validation datasets, LUAD patients with the higher risk score had a poorer prognosis. The nomogram based on risk score showed good performance in prognosis prediction with a C-index of 0.77. The expression levels of ABCC2, ARL2BP, DKK1, LRFN4, PYGL, SMNDC1, and SNAI2 were positively related to the resistance of EGFR-TKI. However, the expression level of FUT1 was favorably correlated with EGFR-TKI responsiveness. The RF model worked wonderfully for distinguishing sensitive and resistant EGFR-TKI samples in the internal and external testing datasets, with predictive area under the curves (AUC) of 0.973 and 0.817, respectively. Conclusion: Our investigation revealed eight genes associated with EGFR-TKI resistance and provided models for EGFR-TKI resistance and prognosis prediction in LUAD patients.
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Then, based on the eight genes, we constructed a random forest model by the “caret” R package (Kuhn, 2008) to distinguish sensitive and resistant EGFR-TKI patients on the training dataset.
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sections[9] "2.7 Construction and validation of the random forest model to distinguish sensitive and resistant EGFR-TKI patients" paragraph 3
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Then, based on the eight genes, we constructed a random forest model by the “caret” R package (Kuhn, 2008) to distinguish sensitive and resistant EGFR-TKI patients on the training dataset.
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sections[24] "Data availability statement" paragraph 2
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
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A random forest model based on eight genes distinguished EGFR-TKI-sensitive from EGFR-TKI-resistant samples with an AUC of 0.973 in internal testing and 0.817 in external testing.
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The RF model worked wonderfully for distinguishing sensitive and resistant EGFR-TKI samples in the internal and external testing datasets, with predictive area under the curves (AUC) of 0.973 and 0.817, respectively.
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A random forest model based on eight genes distinguished EGFR-TKI-sensitive from EGFR-TKI-resistant samples with an AUC of 0.973 in internal testing and 0.817 in external testing.
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Activation of IGFBP7 Drives Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibition in Lung Cancer
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Transcriptomic analysis of gefitinib-resistant EGFR-mutant NSCLC cells
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Gene Expression Patterns that Predict Sensitivity to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Lung Cancer Cell Lines and Human Lung Tumors
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[41]
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[43]
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[44]
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[47]
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[49]
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[50]
GSM1019188
[51]
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[52]
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[53]
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[54]
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[62]
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[63]
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[64]
GSM1019202
[65]
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[67]
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[83]
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[84]
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[85]
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[86]
GSM1019224
[87]
GSM1019225
[88]
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[89]
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[91]
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[92]
GSM1019230
[93]
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[94]
GSM1019232
[95]
GSM1019233
[96]
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[97]
GSM1019235
[98]
GSM1019236
[99]
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[100]
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[101]
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[102]
GSM1019240
[103]
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[104]
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[105]
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[106]
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[107]
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[108]
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[109]
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[110]
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[111]
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[112]
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[113]
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[114]
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[115]
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[116]
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[117]
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[118]
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[119]
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[120]
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[122]
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[143]
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[144]
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GSM1019333
sample_count
196
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Biomarker discovery in non-small cell lung cancer: integrating gene expression profiling, meta-analysis and tissue microarray validation
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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[6] object · 15 fields
id
data:geo:GSE80344
role
raw
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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=GSE80344
sha256
null
bytes
null
access
open
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resolved
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null
reader_status
reader_required
identifier
GSE80344
version
null
note
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
access_statement_kind
data_availability_statement
sample_accessions array · 16 items
[0]
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[1]
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[2]
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[4]
GSM2124850
[5]
GSM2124851
[6]
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[7]
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[9]
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[10]
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[11]
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[12]
GSM2124858
[13]
GSM2124859
[14]
GSM2124860
[15]
GSM2124861
sample_count
16
group_sizes
null
group_sizes_basis
null
platform
16699
taxon
Homo sapiens
title
Gene expression profiling of Erlotinib sensitive and resistant human non small cell lung cancer (NSCLC) cell lines
resolution_checked_at
2026-11-01T18:46:34Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 12 items
[0]
asset:data:geo:GSE122005 not downloaded
[1]
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[2]
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[3]
asset:data:geo:GSE123066 licence not read
[4]
asset:data:geo:GSE31625 not downloaded
[5]
asset:data:geo:GSE31625 licence not read
[6]
asset:data:geo:GSE34228 not downloaded
[7]
asset:data:geo:GSE34228 licence not read
[8]
asset:data:geo:GSE37745 not downloaded
[9]
asset:data:geo:GSE37745 licence not read
[10]
asset:data:geo:GSE80344 not downloaded
[11]
asset:data:geo:GSE80344 licence not read
analysis object · 4 fields
state
partial
methods array · 3 items
[0] object · 10 fields
id
method-1
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machine_learning
specific
random_forest
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Machine learning
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missing_operations array · 1 item
[0]
machine_learning_random_forest
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false
parameters object · 0 fields
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labelled_feature_matrix
evidence object · 3 fields
score
1
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quote
Then, based on the eight genes, we constructed a random forest model by the “caret” R package (Kuhn, 2008) to distinguish sensitive and resistant EGFR-TKI patients on the training dataset.
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method-2
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principal_component_analysis
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Principal component analysis
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wide_numeric_matrix
evidence object · 3 fields
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0.8
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principal component analysis
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id
method-3
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diagnostic_evaluation
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roc
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Diagnostic test evaluation
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confusion_counts
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sensitivity_specificity
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published_precision_envelope
missing_operations array · 0 items
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reference_standard_and_test
evidence object · 3 fields
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0.8
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high
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ROC curve
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[0]
method.reader_differs_from_extractor
[1]
method.machine_learning_random_forest
capability object · 3 fields
state
complete
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[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]
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[4]
pca
[5]
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[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
false
required_operations array · 0 items
missing_operations array · 1 item
[0]
machine_learning_random_forest
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: random_forest.
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 · 6 items
[0]
GSE31625
[1]
GSE34228
[2]
GSE122005
[3]
GSE80344
[4]
GSE123066
[5]
GSE37745
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[0]
GSE31625
[1]
GSE34228
[2]
GSE122005
[3]
GSE80344
[4]
GSE123066
[5]
GSE37745
statements array · 1 item
[0]
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
basis
The paper names GSE31625, GSE34228, GSE122005, GSE80344, GSE123066, GSE37745 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 · 0 items
assets array · 2 items
[0]
source:pmid:36506325
[1]
data:geo:GSE122005
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[0] object · 3 fields
operation
machine_learning_random_forest
priority
null
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[0]
data:geo:GSE122005
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state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
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MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-11-01T18:19:23Z
independence
single_reader
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method
verbatim
availability
verbatim
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5
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10078
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2226
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128
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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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review.independent_reader
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review.machine_critique
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review.human_critique
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absent
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not_run
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null
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pmid:36506325
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paper
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pmid:36506325
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id
source:pmid:36506325
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manuscript
label
PMID 36506325 full text
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id
data:geo:GSE122005
type
dataset
label
GEO GSE122005
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[0] object · 4 fields
id
activity-reading-sci-2026-11-01
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classification
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id
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paper
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pmid:36506325
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id
source:pmid:36506325
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PMID 36506325 full text
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id
data:geo:GSE122005
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dataset
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GEO GSE122005
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agent:corpus-assay-engine
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id
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agent:minimax-reader
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activity-resolve-GSE122005
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data:geo:GSE122005
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agent:corpus-assay-engine
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pmid:36506325
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[0]
Then, based on the eight genes, we constructed a random forest model by the “caret” R package (Kuhn, 2008) to distinguish sensitive and resistant EGFR-TKI patients on the training dataset.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36506325", "kind": "science-record", "revision": 3, "content_hash": "sha256:5ab799a3ac8261da06794961d019d34f71babdf3ae55cb3834263eaaeeb624eb", "created_at": "2026-11-01T19:01:00Z", "updated_at": "2026-11-01T22:08:18Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Construction of the model for predicting prognosis by key genes regulating EGFR-TKI resistance.", "doi": "10.3389/fgene.2022.968376", "pmid": "36506325", "authors": ["Jinke Zhuge", "Xiuqing Wang", "Jingtai Li", "Tongyuan Wang", "Hongkang Wang", "Mingxing Yang", "Wen Dong", "Yong Gao"], "journal": "Frontiers in genetics", "year": 2022, "abstract": "Background: Previous studies have suggested that patients with lung adenocarcinoma (LUAD) will significantly benefit from epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). However, many LUAD patients will develop resistance to EGFR-TKI. Thus, our study aims to develop models to predict EGFR-TKI resistance and the LUAD prognosis. Methods: Two Gene Expression Omnibus (GEO) datasets (GSE31625 and GSE34228) were used as the discovery datasets to find the common differentially expressed genes (DEGs) in EGFR-TKI resistant LUAD profiles. The association of these common DEGs with LUAD prognosis was investigated in The Cancer Genome Atlas (TCGA) database. Moreover, we constructed the risk score for prognosis prediction of LUAD by LASSO analysis. The performance of the risk score for predicting LUAD prognosis was calculated using an independent dataset (GSE37745). A random forest model by risk score genes was trained in the training dataset, and the diagnostic ability for distinguishing sensitive and EGFR-TKI resistant samples was validated in the internal testing dataset and external testing datasets (GSE122005, GSE80344, and GSE123066). Results: From the discovery datasets, 267 common upregulated genes and 374 common downregulated genes were identified. Among these common DEGs, there were 59 genes negatively associated with prognosis, while 21 genes exhibited positive correlations with prognosis. Eight genes (ABCC2, ARL2BP, DKK1, FUT1, LRFN4, PYGL, SMNDC1, and SNAI2) were selected to construct the risk score signature. In both the discovery and independent validation datasets, LUAD patients with the higher risk score had a poorer prognosis. The nomogram based on risk score showed good performance in prognosis prediction with a C-index of 0.77. The expression levels of ABCC2, ARL2BP, DKK1, LRFN4, PYGL, SMNDC1, and SNAI2 were positively related to the resistance of EGFR-TKI. However, the expression level of FUT1 was favorably correlated with EGFR-TKI responsiveness. The RF model worked wonderfully for distinguishing sensitive and resistant EGFR-TKI samples in the internal and external testing datasets, with predictive area under the curves (AUC) of 0.973 and 0.817, respectively. Conclusion: Our investigation revealed eight genes associated with EGFR-TKI resistance and provided models for EGFR-TKI resistance and prognosis prediction in LUAD patients.", "claims": [{"id": "claim-method", "statement": "Then, based on the eight genes, we constructed a random forest model by the “caret” R package (Kuhn, 2008) to distinguish sensitive and resistant EGFR-TKI patients on the training dataset.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36506325", "locator": "sections[9] \"2.7 Construction and validation of the random forest model to distinguish sensitive and resistant EGFR-TKI patients\" paragraph 3", "quote": "Then, based on the eight genes, we constructed a random forest model by the “caret” R package (Kuhn, 2008) to distinguish sensitive and resistant EGFR-TKI patients on the training dataset."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36506325", "locator": "sections[24] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A random forest model based on eight genes distinguished EGFR-TKI-sensitive from EGFR-TKI-resistant samples with an AUC of 0.973 in internal testing and 0.817 in external testing.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36506325", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The RF model worked wonderfully for distinguishing sensitive and resistant EGFR-TKI samples in the internal and external testing datasets, with predictive area under the curves (AUC) of 0.973 and 0.817, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "A random forest model based on eight genes distinguished EGFR-TKI-sensitive from EGFR-TKI-resistant samples with an AUC of 0.973 in internal testing and 0.817 in external testing.", "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:36506325"], "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. 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