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pmid:35371305

Identification and analysis of a prognostic ferroptosis and iron-metabolism signature for esophageal squamous cell carcinoma.

Mengnan Zhao · Ming Li · Yuansheng Zheng · Zhengyang Hu · Jiaqi Liang · Guoshu Bi · Yunyi Bian · Qihai Sui · Cheng Zhan · Miao Lin · Qun Wang

Journal of Cancer · 2022 doi:10.7150/jca.68568

Paper

complete

Experiment

complete

Data

partial

Analysis

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Execution

absent

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pmid:35371305
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title
Identification and analysis of a prognostic ferroptosis and iron-metabolism signature for esophageal squamous cell carcinoma.
doi
10.7150/jca.68568
pmid
35371305
authors array · 11 items
[0]
Mengnan Zhao
[1]
Ming Li
[2]
Yuansheng Zheng
[3]
Zhengyang Hu
[4]
Jiaqi Liang
[5]
Guoshu Bi
[6]
Yunyi Bian
[7]
Qihai Sui
[8]
Cheng Zhan
[9]
Miao Lin
[10]
Qun Wang
journal
Journal of Cancer
year
2022
abstract
Background: The role of ferroptosis in esophageal squamous cell carcinoma (ESCC) is still unclear. Methods: The association of iron metabolism and ferroptosis-related genes with the prognosis, copy number variation (CNV), TMB, and immune cell infiltration of ESCC was explored using data from the GEO and TCGA database and validated by immunofluorescence in 112 ESCC patients from our center. The potential anti-cancer drugs and compounds from the GDSC and the Connectivity Map database were also screened. Results: A total of 117 iron metabolism and ferroptosis-related genes were identified. We found the expressions of PRNP, SLC3A2, SLC39A8, and SLC39A14 negatively related to the prognosis of ESCC patients, while ATP6V0A1 and LCN2 were opposite, which was validated in 112 ESCC samples from our center. And a prognostic signature was constructed based on their expressions and Cox regression coefficient (β). The low-score group exhibited a significantly worse OS. Besides, analysis of 179 ESCC samples from GSE53625 revealed that patients of poorly differentiation, more than 60 years, T4 stage, advanced N stage, advanced stage, and adjuvant therapy also exhibited a significantly shorter OS, based on which a nomogram to predict the OS was established. Moreover, the low-score group exhibited significantly higher CNV and TMB and more frequent mutations of TP53, MUC16, and NOTCH1. Higher proportion of Macrophages M2, and lower proportion of T cells follicular helper were observed in the low-score group. We discovered that AZD7762, Sunitinib, Cytarabine, Docetaxel, Vinblastine, and Elesclomol exhibited lower IC50 in the low-score group. And 20 potential compounds were identified from the CMap database. Conclusions: Six iron metabolism and ferroptosis-related genes were associated with the prognosis, CNV, TMB, and immune cell infiltration of ESCC. Some potential anti-cancer drugs and compounds may be helpful for OS.
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The relation of the expression of DEGs to the prognosis of ESCC patients was analyzed with multivariate Cox regression, based on which a prognostic signature was constructed.
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sections[6] "Construction and functional analysis of iron metabolism and ferroptosis-related prognostic signature" paragraph 2
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The relation of the expression of DEGs to the prognosis of ESCC patients was analyzed with multivariate Cox regression, based on which a prognostic signature was constructed.
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The expression data of ESCC and normal esophageal tissues were extracted from the GSE20347, GSE67269, and GSE38129 datasets.
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sections[5] "Identifying differentially expressed iron metabolism and ferroptosis-related genes (DEGs) between ESCC and normal esophageal tissues" paragraph 2
quote
The expression data of ESCC and normal esophageal tissues were extracted from the GSE20347, GSE67269, and GSE38129 datasets.
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Six iron metabolism and ferroptosis-related genes were associated with the prognosis, CNV, TMB, and immune cell infiltration of ESCC.
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Conclusions: Six iron metabolism and ferroptosis-related genes were associated with the prognosis, CNV, TMB, and immune cell infiltration of ESCC.
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Six iron metabolism and ferroptosis-related genes were associated with the prognosis, CNV, TMB, and immune cell infiltration of ESCC.
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sample_count
358
group_sizes
null
group_sizes_basis
null
platform
18109
taxon
Homo sapiens
title
LncRNA profile study reveals a three-lncRNA signature associated with the survival of esophageal squamous cell carcinoma patients
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[4] object · 15 fields
id
data:geo:GSE67269
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=GSE67269
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE67269
version
null
note
The expression data of ESCC and normal esophageal tissues were extracted from the GSE20347, GSE67269, and GSE38129 datasets.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The expression data of ESCC and normal esophageal tissues were extracted from the GSE20347, GSE67269, and GSE38129 datasets.
access_statement_kind
repository_route_statement
sample_accessions array · 452 items
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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
gaps array · 8 items
[0]
asset:data:geo:GSE20347 not downloaded
[1]
asset:data:geo:GSE20347 licence not read
[2]
asset:data:geo:GSE38129 not downloaded
[3]
asset:data:geo:GSE38129 licence not read
[4]
asset:data:geo:GSE53625 not downloaded
[5]
asset:data:geo:GSE53625 licence not read
[6]
asset:data:geo:GSE67269 not downloaded
[7]
asset:data:geo:GSE67269 licence not read
analysis object · 4 fields
state
complete
methods array · 1 item
[0] object · 10 fields
id
method-1
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
1
band
verbatim
quote
The relation of the expression of DEGs to the prognosis of ESCC patients was analyzed with multivariate Cox regression, based on which a prognostic signature was constructed.
targets array · 0 items
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 1 item
[0]
cox_ph
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: cox_proportional_hazards.
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]
GSE20347
[1]
GSE67269
[2]
GSE38129
[3]
GSE53625
resolved_accessions array · 4 items
[0]
GSE20347
[1]
GSE67269
[2]
GSE38129
[3]
GSE53625
statements array · 1 item
[0]
The expression data of ESCC and normal esophageal tissues were extracted from the GSE20347, GSE67269, and GSE38129 datasets.
basis
The paper names GSE20347, GSE67269, GSE38129, GSE53625 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 1 item
[0]
cox_ph
assets array · 2 items
[0]
source:pmid:35371305
[1]
data:geo:GSE20347
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:GSE20347
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
2026-11-01T17:40:42Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
null
calls
5
usage object · 3 fields
prompt_tokens
8773
completion_tokens
2618
cached_tokens
128
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:35371305
type
paper
label
pmid:35371305
[1] object · 3 fields
id
source:pmid:35371305
type
manuscript
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PMID 35371305 full text
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he "survminer" R package, based on which the patients were divided into low- and high-score group 10. T
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al cut-off score, based on which the 96 ESCC patients were divided into high- and low-score group. The
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g/gsea/index.jsp) 11. Cell culture and siRNA transfection Two ESCC cell lines (KYSE150 and ECA109) wer
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uangzhou, China) (Table S1). The siRNAs were transfected into cells with Lipo8000 transfect reagent (
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essions of the above 6 prognostic genes were knock-down with 2 diiferent small interfering RNAs (siR
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gdb.org/gsea/index.jsp) 11. Cell culture and siRNA transfection Two ESCC cell lines (KYSE150 an
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The relation of the expression of DEGs to the prognosis of ESCC patients was analyzed with multivariate Cox regression, based on which a prognostic signature was constructed.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35371305", "kind": "science-record", "revision": 3, "content_hash": "sha256:f55a946a5a21467b9b96ba4189c647895165665b55d4f142f6803d95c90e23fa", "created_at": "2026-11-01T18:14:11Z", "updated_at": "2026-11-01T21:27:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and analysis of a prognostic ferroptosis and iron-metabolism signature for esophageal squamous cell carcinoma.", "doi": "10.7150/jca.68568", "pmid": "35371305", "authors": ["Mengnan Zhao", "Ming Li", "Yuansheng Zheng", "Zhengyang Hu", "Jiaqi Liang", "Guoshu Bi", "Yunyi Bian", "Qihai Sui", "Cheng Zhan", "Miao Lin", "Qun Wang"], "journal": "Journal of Cancer", "year": 2022, "abstract": "Background: The role of ferroptosis in esophageal squamous cell carcinoma (ESCC) is still unclear. Methods: The association of iron metabolism and ferroptosis-related genes with the prognosis, copy number variation (CNV), TMB, and immune cell infiltration of ESCC was explored using data from the GEO and TCGA database and validated by immunofluorescence in 112 ESCC patients from our center. The potential anti-cancer drugs and compounds from the GDSC and the Connectivity Map database were also screened. Results: A total of 117 iron metabolism and ferroptosis-related genes were identified. We found the expressions of PRNP, SLC3A2, SLC39A8, and SLC39A14 negatively related to the prognosis of ESCC patients, while ATP6V0A1 and LCN2 were opposite, which was validated in 112 ESCC samples from our center. And a prognostic signature was constructed based on their expressions and Cox regression coefficient (β). The low-score group exhibited a significantly worse OS. Besides, analysis of 179 ESCC samples from GSE53625 revealed that patients of poorly differentiation, more than 60 years, T4 stage, advanced N stage, advanced stage, and adjuvant therapy also exhibited a significantly shorter OS, based on which a nomogram to predict the OS was established. Moreover, the low-score group exhibited significantly higher CNV and TMB and more frequent mutations of TP53, MUC16, and NOTCH1. Higher proportion of Macrophages M2, and lower proportion of T cells follicular helper were observed in the low-score group. We discovered that AZD7762, Sunitinib, Cytarabine, Docetaxel, Vinblastine, and Elesclomol exhibited lower IC50 in the low-score group. And 20 potential compounds were identified from the CMap database. Conclusions: Six iron metabolism and ferroptosis-related genes were associated with the prognosis, CNV, TMB, and immune cell infiltration of ESCC. Some potential anti-cancer drugs and compounds may be helpful for OS.", "claims": [{"id": "claim-method", "statement": "The relation of the expression of DEGs to the prognosis of ESCC patients was analyzed with multivariate Cox regression, based on which a prognostic signature was constructed.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35371305", "locator": "sections[6] \"Construction and functional analysis of iron metabolism and ferroptosis-related prognostic signature\" paragraph 2", "quote": "The relation of the expression of DEGs to the prognosis of ESCC patients was analyzed with multivariate Cox regression, based on which a prognostic signature was constructed."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The expression data of ESCC and normal esophageal tissues were extracted from the GSE20347, GSE67269, and GSE38129 datasets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35371305", "locator": "sections[5] \"Identifying differentially expressed iron metabolism and ferroptosis-related genes (DEGs) between ESCC and normal esophageal tissues\" paragraph 2", "quote": "The expression data of ESCC and normal esophageal tissues were extracted from the GSE20347, GSE67269, and GSE38129 datasets."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Six iron metabolism and ferroptosis-related genes were associated with the prognosis, CNV, TMB, and immune cell infiltration of ESCC.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35371305", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Conclusions: Six iron metabolism and ferroptosis-related genes were associated with the prognosis, CNV, TMB, and immune cell infiltration of ESCC."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Six iron metabolism and ferroptosis-related genes were associated with the prognosis, CNV, TMB, and immune cell infiltration of ESCC.", "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:35371305"], "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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T", "al cut-off score, based on which the 96 ESCC patients were divided into high- and low-score group. The"], "order_basis": "paper_text_order:2766", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["g/gsea/index.jsp) 11. Cell culture and siRNA transfection Two ESCC cell lines (KYSE150 and ECA109) wer", "uangzhou, China) (Table S1). The siRNAs were transfected into cells with Lipo8000 transfect reagent (", "essions of the above 6 prognostic genes were knock-down with 2 diiferent small interfering RNAs (siR", "gdb.org/gsea/index.jsp) 11. 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