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pmid:35342303

Analysis of Ferroptosis-Related LncRNAs Signatures Associated with Tumor Immune Infiltration and Experimental Validation in Clear Cell Renal Cell Carcinoma.

Xinyi Chen · Jingyao Tu · Li Ma · Yongbiao Huang · Chunguang Yang · Xianglin Yuan

International journal of general medicine · 2022 doi:10.2147/IJGM.S354682

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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title
Analysis of Ferroptosis-Related LncRNAs Signatures Associated with Tumor Immune Infiltration and Experimental Validation in Clear Cell Renal Cell Carcinoma.
doi
10.2147/IJGM.S354682
pmid
35342303
authors array · 6 items
[0]
Xinyi Chen
[1]
Jingyao Tu
[2]
Li Ma
[3]
Yongbiao Huang
[4]
Chunguang Yang
[5]
Xianglin Yuan
journal
International journal of general medicine
year
2022
abstract
Background: Clear cell renal cell carcinoma (ccRCC) is the most aggressive subtype of renal cell carcinoma. Ferroptosis is an iron-dependent programmed cell death. Long non-coding RNAs (lncRNAs) emerge as a critical role in regulating cancer progression. Objective: This study aimed to identify molecular regulation of ferroptosis-related lncRNAs (FRLs) in ccRCC. Methods: The prognostic value of FRLs was investigated in ccRCC samples downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset. The FRLs were screened out by Pearson correlation test. The 465 FRLs confirmed as potential prognostic factors through univariate Cox regression analysis were entered into Lasso and multivariate Cox regression to build a FRLs prognostic signature. A risk score based on the prognostic model divided ccRCC patients into low- and high-risk groups. A prognostic nomogram, derived from the prognostic signature and integrating clinical characteristics, was constructed. Gene set enrichment analysis (GSEA) revealed the immune- and tumor-associated pathways. Two distinct clusters were identified with different immune signatures through consensus clustering analysis. The prognostic value of some hub FRLs was externally validated via three GEO datasets (GSE46699, GSE53757 and GSE66272) and online databases. Finally, the three FRLs (LINC00460, LINC00941 and LINC02027) were verified through in vitro experiments. Results: The FRLs prognostic signature, including 7 independent prognostic lncRNAs, exhibited good accuracy in predicting overall survival (OS) of ccRCC patients. This signature was correlated with immune infiltration and immune checkpoint blockade (ICB). We correlated two distinct clusters with immune infiltration signature of ccRCC. The worse prognosis of cluster 2 was probably mediated by immune evasion. We also found that the expression levels of LINC00460 and LINC00941 in ccRCC cell lines were higher than those in HK-2 cells, but LINC02027 showed the inverse trend. Conclusion: Collectively, our study demonstrated a FRLs prognostic signature which had great clinical value in prognosis assessment.
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The FRLs were screened out by Pearson correlation test.
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Raw data are available at TCGA (search term: TCGA-KIRC). TCGA belongs to public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles.
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The FRLs prognostic signature, including 7 independent prognostic lncRNAs, exhibited good accuracy in predicting overall survival (OS) of ccRCC patients.
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The FRLs prognostic signature, including 7 independent prognostic lncRNAs, exhibited good accuracy in predicting overall survival (OS) of ccRCC patients.
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The FRLs prognostic signature, including 7 independent prognostic lncRNAs, exhibited good accuracy in predicting overall survival (OS) of ccRCC patients.
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Smoking and Obesity Related Molecular Alterations in Clear Cell Renal Cell Carcinoma
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0.8
band
high
quote
GO enrichment
[4] object · 10 fields
id
method-5
family
contingency_analysis
specific
chi_square
label
Categorical (contingency table) analysis
dsl_operations array · 1 item
[0]
chi_square_test
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
categorical_cross_tabulation
evidence object · 3 fields
score
0.8
band
high
quote
Chi-square
targets array · 0 items
gaps array · 1 item
[0]
method.reader_differs_from_extractor
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 1 item
[0]
pearson_r
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: pearson.
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 · 3 items
[0]
GSE46699
[1]
GSE53757
[2]
GSE66272
resolved_accessions array · 3 items
[0]
GSE46699
[1]
GSE53757
[2]
GSE66272
statements array · 1 item
[0]
Raw data are available at TCGA (search term: TCGA-KIRC). TCGA belongs to public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles.
basis
The paper names GSE46699, GSE53757, GSE66272 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 · 1 item
[0]
pearson_r
assets array · 2 items
[0]
source:pmid:35342303
[1]
data:geo:GSE46699
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:GSE46699
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
2026-11-01T17:39:37Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
16970
completion_tokens
2260
cached_tokens
264
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:35342303
type
paper
label
pmid:35342303
[1] object · 3 fields
id
source:pmid:35342303
type
manuscript
label
PMID 35342303 full text
[2] object · 3 fields
id
data:geo:GSE46699
type
dataset
label
GEO GSE46699
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:35342303
type
paper
label
pmid:35342303
[1] object · 3 fields
id
source:pmid:35342303
type
manuscript
label
PMID 35342303 full text
[2] object · 3 fields
id
data:geo:GSE46699
type
dataset
label
GEO GSE46699
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-35342303
type
extraction
used array · 1 item
[0]
source:pmid:35342303
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE46699
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE46699
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
label
Corpus assay engine
[1] object · 3 fields
id
agent:minimax-reader
type
software
label
MiniMax literature reader
source_run_id
reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
snapshot_id
ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:35342303
parent_hash
sha256:c5198bb8d7c244d2f9793c7153c0300c1acb988a35e7c2ac0a46f555771dde45
fork_of
null
gaps array · 11 items
[0]
asset:data:geo:GSE46699 licence not read
[1]
asset:data:geo:GSE46699 not downloaded
[2]
asset:data:geo:GSE53757 licence not read
[3]
asset:data:geo:GSE53757 not downloaded
[4]
asset:data:geo:GSE66272 licence not read
[5]
asset:data:geo:GSE66272 not downloaded
[6]
execution.not_run
[7]
method.reader_differs_from_extractor
[8]
review.human_critique
[9]
review.independent_reader
[10]
review.machine_critique
assays array · 3 items
[0] object · 11 fields
role
data_generation
definition_id
cell_culture
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.77
evidence array · 1 item
[0]
a humid 5% CO2 environment and was routinely cultured in RPMI 1640 or DMEM supplemented with 10% feta
order_basis
paper_text_order:2623
id
assay:1
[1] object · 11 fields
role
data_generation
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 4 items
[0]
ifferentially expressed FRLs. The results of RT-qPCR showed that the overall trend in the express
[1]
he expression levels of FRLs in vitro. (A–C) RT-qPCR was used to measure the mRNA level of LINC00
[2]
erentially expressed FRLs. The results of RT-qPCR showed that the overall trend in the express
[3]
expression levels of FRLs in vitro. (A–C) RT-qPCR was used to measure the mRNA level of LINC00
order_basis
paper_text_order:7403
id
assay:2
[2] object · 11 fields
role
analysis
definition_id
correlation_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
pearson_r
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
The FRLs were screened out by Pearson correlation test.
order_basis
consumes_earlier_output
id
assay:3
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35342303", "kind": "science-record", "revision": 3, "content_hash": "sha256:20910683d8bf0d17ed6caa2aaf675a34acfc1fc9f7832f1235dc72f9441cfaaa", "created_at": "2026-11-01T18:14:08Z", "updated_at": "2026-11-01T21:27:31Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Analysis of Ferroptosis-Related LncRNAs Signatures Associated with Tumor Immune Infiltration and Experimental Validation in Clear Cell Renal Cell Carcinoma.", "doi": "10.2147/IJGM.S354682", "pmid": "35342303", "authors": ["Xinyi Chen", "Jingyao Tu", "Li Ma", "Yongbiao Huang", "Chunguang Yang", "Xianglin Yuan"], "journal": "International journal of general medicine", "year": 2022, "abstract": "Background: Clear cell renal cell carcinoma (ccRCC) is the most aggressive subtype of renal cell carcinoma. Ferroptosis is an iron-dependent programmed cell death. Long non-coding RNAs (lncRNAs) emerge as a critical role in regulating cancer progression.\nObjective: This study aimed to identify molecular regulation of ferroptosis-related lncRNAs (FRLs) in ccRCC.\nMethods: The prognostic value of FRLs was investigated in ccRCC samples downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset. The FRLs were screened out by Pearson correlation test. The 465 FRLs confirmed as potential prognostic factors through univariate Cox regression analysis were entered into Lasso and multivariate Cox regression to build a FRLs prognostic signature. A risk score based on the prognostic model divided ccRCC patients into low- and high-risk groups. A prognostic nomogram, derived from the prognostic signature and integrating clinical characteristics, was constructed. Gene set enrichment analysis (GSEA) revealed the immune- and tumor-associated pathways. Two distinct clusters were identified with different immune signatures through consensus clustering analysis. The prognostic value of some hub FRLs was externally validated via three GEO datasets (GSE46699, GSE53757 and GSE66272) and online databases. Finally, the three FRLs (LINC00460, LINC00941 and LINC02027) were verified through in vitro experiments.\nResults: The FRLs prognostic signature, including 7 independent prognostic lncRNAs, exhibited good accuracy in predicting overall survival (OS) of ccRCC patients. This signature was correlated with immune infiltration and immune checkpoint blockade (ICB). We correlated two distinct clusters with immune infiltration signature of ccRCC. The worse prognosis of cluster 2 was probably mediated by immune evasion. We also found that the expression levels of LINC00460 and LINC00941 in ccRCC cell lines were higher than those in HK-2 cells, but LINC02027 showed the inverse trend.\nConclusion: Collectively, our study demonstrated a FRLs prognostic signature which had great clinical value in prognosis assessment.", "claims": [{"id": "claim-method", "statement": "The FRLs were screened out by Pearson correlation test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35342303", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The FRLs were screened out by Pearson correlation test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Raw data are available at TCGA (search term: TCGA-KIRC). TCGA belongs to public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35342303", "locator": "sections[27] \"Data Sharing Statement\" paragraph 2", "quote": "Raw data are available at TCGA (search term: TCGA-KIRC). TCGA belongs to public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The FRLs prognostic signature, including 7 independent prognostic lncRNAs, exhibited good accuracy in predicting overall survival (OS) of ccRCC patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35342303", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "The FRLs prognostic signature, including 7 independent prognostic lncRNAs, exhibited good accuracy in predicting overall survival (OS) of ccRCC patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The FRLs prognostic signature, including 7 independent prognostic lncRNAs, exhibited good accuracy in predicting overall survival (OS) of ccRCC patients.", "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:35342303"], "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:GSE46699"], "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:GSE46699"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35342303", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/IJGM.S354682", "sha256": "sha256:a264fc6101e88c5f2c3ebef98f72f560cd73374fee193a2a321882ea3b642e2d", "bytes": 61592, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/IJGM.S354682", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8942346", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE46699", "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=GSE46699", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE46699", "version": null, "note": "Raw data are available at TCGA (search term: TCGA-KIRC). TCGA belongs to public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Raw data are available at TCGA (search term: TCGA-KIRC). TCGA belongs to public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1134764", "GSM1134765", "GSM1134766", "GSM1134767", "GSM1134768", "GSM1134769", "GSM1134770", "GSM1134771", "GSM1134772", "GSM1134773", "GSM1134774", "GSM1134775", "GSM1134776", "GSM1134777", "GSM1134778", "GSM1134779", "GSM1134780", "GSM1134781", "GSM1134782", "GSM1134783", "GSM1134784", "GSM1134785", "GSM1134786", "GSM1134787", "GSM1134788", "GSM1134789", "GSM1134790", "GSM1134791", "GSM1134792", "GSM1134793", "GSM1134794", "GSM1134795", "GSM1134796", "GSM1134797", "GSM1134798", "GSM1134799", "GSM1134800", "GSM1134801", "GSM1134802", "GSM1134803", "GSM1134804", "GSM1134805", "GSM1134806", "GSM1134807", "GSM1134808", "GSM1134809", "GSM1134810", "GSM1134811", "GSM1134812", "GSM1134813", "GSM1134814", "GSM1134815", "GSM1134816", "GSM1134817", "GSM1134818", "GSM1134819", "GSM1134820", "GSM1134821", "GSM1134822", "GSM1134823", "GSM1134824", "GSM1134825", "GSM1134826", "GSM1134827", "GSM1134828", "GSM1134829", "GSM1134830", "GSM1134831", "GSM1134832", "GSM1134833", "GSM1134834", "GSM1134835", "GSM1134836", "GSM1134837", "GSM1134838", "GSM1134839", "GSM1134840", "GSM1134841", "GSM1134842", "GSM1134843", "GSM1134844", "GSM1134845", "GSM1134846", "GSM1134847", "GSM1134848", "GSM1134849", "GSM1134850", "GSM1134851", "GSM1134852", "GSM1134853", "GSM1134854", "GSM1134855", "GSM1134856", "GSM1134857", "GSM1134858", "GSM1134859", "GSM1134860", "GSM1134861", "GSM1134862", "GSM1134863", "GSM1134864", "GSM1134865", "GSM1134866", "GSM1134867", "GSM1134868", "GSM1134869", "GSM1134870", "GSM1134871", "GSM1134872", "GSM1134873", "GSM1134874", "GSM1134875", "GSM1134876", "GSM1134877", "GSM1134878", "GSM1134879", "GSM1134880", "GSM1134881", "GSM1134882", "GSM1134883", "GSM1134884", "GSM1134885", "GSM1134886", "GSM1134887", "GSM1134888", "GSM1134889", "GSM1304420", "GSM1304421", "GSM1304422", "GSM1304423"], "sample_count": 130, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Smoking and Obesity Related Molecular Alterations in Clear Cell Renal Cell Carcinoma", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE53757", "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=GSE53757", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE53757", "version": null, "note": "Raw data are available at TCGA (search term: TCGA-KIRC). TCGA belongs to public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Raw data are available at TCGA (search term: TCGA-KIRC). TCGA belongs to public databases. The patients involved in the database have obtained ethical approval. 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