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pmid:34456964

Identification of Key Genes and Pathways Associated With Paclitaxel Resistance in Esophageal Squamous Cell Carcinoma Based on Bioinformatics Analysis.

Zhimin Shen · Mingduan Chen · Fei Luo · Hui Xu · Peipei Zhang · Jihong Lin · Mingqiang Kang

Frontiers in genetics · 2021 doi:10.3389/fgene.2021.671639

Paper

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Experiment

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Data

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Analysis

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pmid:34456964
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title
Identification of Key Genes and Pathways Associated With Paclitaxel Resistance in Esophageal Squamous Cell Carcinoma Based on Bioinformatics Analysis.
doi
10.3389/fgene.2021.671639
pmid
34456964
authors array · 7 items
[0]
Zhimin Shen
[1]
Mingduan Chen
[2]
Fei Luo
[3]
Hui Xu
[4]
Peipei Zhang
[5]
Jihong Lin
[6]
Mingqiang Kang
journal
Frontiers in genetics
year
2021
abstract
Esophageal squamous cell carcinoma (ESCC) ranks as the fourth leading cause of cancer-related death in China. Although paclitaxel has been shown to be effective in treating ESCC, the prolonged use of this chemical will lead to paclitaxel resistance. In order to uncover genes and pathways driving paclitaxel resistance in the progression of ESCC, bioinformatics analyses were performed based on The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database including GSE86099 and GSE161533. Differential expression analysis was performed in TCGA data and two GEO datasets to obtain differentially expressed genes (DEGs). Based on GSE161533, weighted gene co-expression network analysis (WGCNA) was conducted to identify the key modules associated with ESCC tumor status. The DEGs common to the two GEO datasets and the genes in the key modules were intersected to obtain the paclitaxel resistance-specific or non-paclitaxel resistance-specific genes, which were subjected to subsequent least absolute shrinkage and selection operator (LASSO) feature selection, whereby paclitaxel resistance-specific or non-paclitaxel resistance-specific key genes were selected. Ten machine learning models were used to validate the biological significance of these key genes; the potential therapeutic drugs for paclitaxel resistance-specific genes were also predicted. As a result, we identified 24 paclitaxel resistance-specific genes and 18 non-paclitaxel resistance-specific genes. The ESCC machine classifiers based on the key genes achieved a relatively high AUC value in the cross-validation and in an independent test set, GSE164158. A total of 207 drugs (such as bevacizumab) were predicted to be alternative therapeutics for ESCC patients with paclitaxel resistance. These results might shed light on the in-depth research of paclitaxel resistance in the context of ESCC progression.
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The least absolute shrinkage and selection operator (LASSO) was adopted to identify the important features of paclitaxel resistance and non-paclitaxel resistance. The R “glmnet” (https://glmnet.stanford.edu) package was used to perform the LASSO selection with 10-fold cross-validation.
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sections[6] "Identification of Key Genes Using LASSO" paragraph 2
quote
The least absolute shrinkage and selection operator (LASSO) was adopted to identify the important features of paclitaxel resistance and non-paclitaxel resistance. The R “glmnet” (https://glmnet.stanford.edu) package was used to perform the LASSO selection with 10-fold cross-validation.
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Publicly available datasets were analyzed in this study. This data can be found at: GSE67269, GSE86099, and GSE161533 from TCGA database.
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sections[19] "Data Availability Statement" paragraph 2
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Publicly available datasets were analyzed in this study. This data can be found at: GSE67269, GSE86099, and GSE161533 from TCGA database.
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[324]
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[325]
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[326]
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[327]
GSM1643395
[328]
GSM1643396
[329]
GSM1643397
[330]
GSM1643398
[331]
GSM1643399
[332]
GSM1643400
[333]
GSM1643401
[334]
GSM1643402
[335]
GSM1643403
[336]
GSM1643404
[337]
GSM1643405
[338]
GSM1643406
[339]
GSM1643407
[340]
GSM1643408
[341]
GSM1643409
[342]
GSM1643410
[343]
GSM1643411
[344]
GSM1643412
[345]
GSM1643413
[346]
GSM1643414
[347]
GSM1643415
[348]
GSM1643416
[349]
GSM1643417
[350]
GSM1643418
[351]
GSM1643419
[352]
GSM1643420
[353]
GSM1643421
[354]
GSM1643422
[355]
GSM1643423
[356]
GSM1643424
[357]
GSM1643425
[358]
GSM1643426
[359]
GSM1643427
[360]
GSM1643428
[361]
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[362]
GSM1643430
[363]
GSM1643431
[364]
GSM1643432
[365]
GSM1643433
[366]
GSM1643434
[367]
GSM1643435
[368]
GSM1643436
[369]
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[370]
GSM1643438
[371]
GSM1643439
[372]
GSM1643440
[373]
GSM1643441
[374]
GSM1643442
[375]
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[376]
GSM1643444
[377]
GSM1643445
[378]
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[379]
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[380]
GSM1643448
[381]
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[382]
GSM1643450
[383]
GSM1643451
[384]
GSM1643452
[385]
GSM1643453
[386]
GSM1643454
[387]
GSM1643455
[388]
GSM1643456
[389]
GSM1643457
[390]
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[391]
GSM1643459
[392]
GSM1643460
[393]
GSM1643461
[394]
GSM1643462
[395]
GSM1643463
[396]
GSM1643464
[397]
GSM1643465
[398]
GSM1643466
[399]
GSM1643467
[400]
GSM1643468
[401]
GSM1643469
[402]
GSM1643470
[403]
GSM1643471
[404]
GSM1643472
[405]
GSM1643473
[406]
GSM1643474
[407]
GSM1643475
[408]
GSM1643476
[409]
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[410]
GSM1643478
[411]
GSM1643479
[412]
GSM1643480
[413]
GSM1643481
[414]
GSM1643482
[415]
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[416]
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[417]
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[418]
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[419]
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[420]
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[421]
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[422]
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[423]
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[424]
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[425]
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[426]
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[427]
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[428]
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[429]
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[430]
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[431]
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[432]
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[433]
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[434]
GSM1643502
[435]
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[436]
GSM1643504
[437]
GSM1643505
[438]
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[439]
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[440]
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[441]
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[442]
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[443]
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[444]
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[445]
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[446]
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[447]
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[448]
GSM1643516
[449]
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[450]
GSM1643518
[451]
GSM1643519
sample_count
452
group_sizes
null
group_sizes_basis
null
platform
571;96;19823;570
taxon
Homo sapiens
title
Integrative analysis of miRNAs and matched gene expression in ESCC
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[4] object · 15 fields
id
data:geo:GSE86099
role
raw
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geo-series
media_type
application/vnd.ncbi.geo-series+json
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE86099
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE86099
version
null
note
Publicly available datasets were analyzed in this study. This data can be found at: GSE67269, GSE86099, and GSE161533 from TCGA database.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
Publicly available datasets were analyzed in this study. This data can be found at: GSE67269, GSE86099, and GSE161533 from TCGA database.
access_statement_kind
data_availability_statement
sample_accessions array · 4 items
[0]
GSM2293542
[1]
GSM2293543
[2]
GSM2293544
[3]
GSM2293545
sample_count
4
group_sizes
null
group_sizes_basis
null
platform
4133
taxon
Homo sapiens
title
Gene expression signature of paclitaxel resistance in human esophageal squamous cell cancer cell line
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 · 8 items
[0]
asset:data:geo:GSE161533 not downloaded
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asset:data:geo:GSE161533 licence not read
[2]
asset:data:geo:GSE164158 not downloaded
[3]
asset:data:geo:GSE164158 licence not read
[4]
asset:data:geo:GSE67269 not downloaded
[5]
asset:data:geo:GSE67269 licence not read
[6]
asset:data:geo:GSE86099 not downloaded
[7]
asset:data:geo:GSE86099 licence not read
analysis object · 4 fields
state
partial
methods array · 2 items
[0] object · 10 fields
id
method-1
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
0.8
band
high
quote
PPI
[1] object · 10 fields
id
method-2
family
null
specific
null
label
Least absolute shrinkage and selection operator (LASSO)
dsl_operations array · 0 items
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 0 items
evidence object · 3 fields
score
1
band
verbatim
quote
The least absolute shrinkage and selection operator (LASSO) was adopted to identify the important features of paclitaxel resistance and non-paclitaxel resistance. The R “glmnet” (https://glmnet.stanford.edu) package was used to perform the LASSO selection with 10-fold cross-validation.
targets array · 0 items
gaps array · 1 item
[0]
method.reader_named_unmapped
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]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
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: ppi_network.
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]
GSE86099
[1]
GSE161533
[2]
GSE164158
[3]
GSE67269
resolved_accessions array · 4 items
[0]
GSE86099
[1]
GSE161533
[2]
GSE164158
[3]
GSE67269
statements array · 1 item
[0]
Publicly available datasets were analyzed in this study. This data can be found at: GSE67269, GSE86099, and GSE161533 from TCGA database.
basis
The paper names GSE86099, GSE161533, GSE164158, GSE67269 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]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
assets array · 2 items
[0]
source:pmid:34456964
[1]
data:geo:GSE161533
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:GSE161533
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
2026-10-31T18:34:21Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
37408
completion_tokens
2977
cached_tokens
784
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
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MiniMax-M3.1-Flash
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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
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gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:34456964
type
paper
label
pmid:34456964
[1] object · 3 fields
id
source:pmid:34456964
type
manuscript
label
PMID 34456964 full text
[2] object · 3 fields
id
data:geo:GSE161533
type
dataset
label
GEO GSE161533
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:34456964
type
paper
label
pmid:34456964
[1] object · 3 fields
id
source:pmid:34456964
type
manuscript
label
PMID 34456964 full text
[2] object · 3 fields
id
data:geo:GSE161533
type
dataset
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GEO GSE161533
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-34456964
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extraction
used array · 1 item
[0]
source:pmid:34456964
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE161533
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accession_resolution
used array · 1 item
[0]
data:geo:GSE161533
agent
agent:corpus-assay-engine
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[0] object · 3 fields
id
agent:corpus-assay-engine
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software
label
Corpus assay engine
[1] object · 3 fields
id
agent:minimax-reader
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software
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MiniMax literature reader
source_run_id
reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
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ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:34456964
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sha256:4f2e9a235cf817a25bae2a707d70fe9e20125bda33ee621b5edf10d8b43a8f27
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null
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asset:data:geo:GSE161533 licence not read
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[3]
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[4]
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[5]
asset:data:geo:GSE67269 not downloaded
[6]
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execution.not_run
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[12]
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assays array · 1 item
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analysis
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network_analysis
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f2132e96ae6c7a4e
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[1]
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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:34456964", "kind": "science-record", "revision": 7, "content_hash": "sha256:a6189f419cc16cac11b3cfcc457d790b8d19ab8b447ba9bd14121e6e845f85f4", "created_at": "2026-11-01T15:41:50Z", "updated_at": "2026-11-01T22:04:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Key Genes and Pathways Associated With Paclitaxel Resistance in Esophageal Squamous Cell Carcinoma Based on Bioinformatics Analysis.", "doi": "10.3389/fgene.2021.671639", "pmid": "34456964", "authors": ["Zhimin Shen", "Mingduan Chen", "Fei Luo", "Hui Xu", "Peipei Zhang", "Jihong Lin", "Mingqiang Kang"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "Esophageal squamous cell carcinoma (ESCC) ranks as the fourth leading cause of cancer-related death in China. Although paclitaxel has been shown to be effective in treating ESCC, the prolonged use of this chemical will lead to paclitaxel resistance. In order to uncover genes and pathways driving paclitaxel resistance in the progression of ESCC, bioinformatics analyses were performed based on The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database including GSE86099 and GSE161533. Differential expression analysis was performed in TCGA data and two GEO datasets to obtain differentially expressed genes (DEGs). Based on GSE161533, weighted gene co-expression network analysis (WGCNA) was conducted to identify the key modules associated with ESCC tumor status. The DEGs common to the two GEO datasets and the genes in the key modules were intersected to obtain the paclitaxel resistance-specific or non-paclitaxel resistance-specific genes, which were subjected to subsequent least absolute shrinkage and selection operator (LASSO) feature selection, whereby paclitaxel resistance-specific or non-paclitaxel resistance-specific key genes were selected. Ten machine learning models were used to validate the biological significance of these key genes; the potential therapeutic drugs for paclitaxel resistance-specific genes were also predicted. As a result, we identified 24 paclitaxel resistance-specific genes and 18 non-paclitaxel resistance-specific genes. The ESCC machine classifiers based on the key genes achieved a relatively high AUC value in the cross-validation and in an independent test set, GSE164158. A total of 207 drugs (such as bevacizumab) were predicted to be alternative therapeutics for ESCC patients with paclitaxel resistance. These results might shed light on the in-depth research of paclitaxel resistance in the context of ESCC progression.", "claims": [{"id": "claim-method", "statement": "The least absolute shrinkage and selection operator (LASSO) was adopted to identify the important features of paclitaxel resistance and non-paclitaxel resistance. The R “glmnet” (https://glmnet.stanford.edu) package was used to perform the LASSO selection with 10-fold cross-validation.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34456964", "locator": "sections[6] \"Identification of Key Genes Using LASSO\" paragraph 2", "quote": "The least absolute shrinkage and selection operator (LASSO) was adopted to identify the important features of paclitaxel resistance and non-paclitaxel resistance. The R “glmnet” (https://glmnet.stanford.edu) package was used to perform the LASSO selection with 10-fold cross-validation."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found at: GSE67269, GSE86099, and GSE161533 from TCGA database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34456964", "locator": "sections[19] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found at: GSE67269, GSE86099, and GSE161533 from TCGA database."}], "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:34456964"], "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:GSE161533"], "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:GSE161533"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34456964", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2021.671639", "sha256": "sha256:1133eeafab0a5fecc63abae6b800023419b8d68b66062b0f5277b7a681816e39", "bytes": 49222, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2021.671639", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8386171", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE161533", "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=GSE161533", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE161533", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found at: GSE67269, GSE86099, and GSE161533 from TCGA database.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. 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