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pmid:35992780

Elevated expression of LIF predicts a poor prognosis and promotes cell migration and invasion of clear cell renal cell carcinoma.

Wenting Zhong · Hongxia Liu · Feng Li · Youyu Lin · Yan Ye · Luyun Xu · ShengZhao Li · Hui Chen · Chengcheng Li · Yuxuan Lin · Wei Zhuang · Yao Lin · Qingshui Wang

Frontiers in oncology · 2022 doi:10.3389/fonc.2022.934128

Paper

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Experiment

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title
Elevated expression of LIF predicts a poor prognosis and promotes cell migration and invasion of clear cell renal cell carcinoma.
doi
10.3389/fonc.2022.934128
pmid
35992780
authors array · 13 items
[0]
Wenting Zhong
[1]
Hongxia Liu
[2]
Feng Li
[3]
Youyu Lin
[4]
Yan Ye
[5]
Luyun Xu
[6]
ShengZhao Li
[7]
Hui Chen
[8]
Chengcheng Li
[9]
Yuxuan Lin
[10]
Wei Zhuang
[11]
Yao Lin
[12]
Qingshui Wang
journal
Frontiers in oncology
year
2022
abstract
Background: Renal cell carcinoma (RCC) is the seventh most common cancer in humans, of which clear cell renal cell carcinoma (ccRCC) accounts for the majority. Recently, although there have been significant breakthroughs in the treatment of ccRCC, the prognosis of targeted therapy is still poor. Leukemia inhibitory factor (LIF) is a pleiotropic protein, which is overexpressed in many cancers and plays a carcinogenic role. In this study, we explored the expression and potential role of LIF in ccRCC. Methods: The expression levels and prognostic effects of the LIF gene in ccRCC were detected using TCGA, GEO, ICGC, and ArrayExpress databases. The function of LIF in ccRCC was investigated using a series of cell function approaches. LIF-related genes were identified by weighted gene correlation network analysis (WGCNA). GO and KEGG analyses were performed subsequently. Cox univariate and LASSO analyses were used to develop risk signatures based on LIF-related genes, and the prognostic model was validated in the ICGC and E-MTAB-1980 databases. Then, a nomogram model was constructed for survival prediction and validation of ccRCC patients. To further explore the drug sensitivity between LIF-related genes, we also conducted a drug sensitivity analysis based on the GDSC database. Results: The mRNA and protein expression levels of LIF were significantly increased in ccRCC patients. In addition, a high expression of LIF has a poor prognostic effect in ccRCC patients. LIF knockdown can inhibit the migration and invasion of ccRCC cells. By using WGCNA, 97 LIF-related genes in ccRCC were identified. Next, a prognostic risk prediction model including eight LIF-related genes (TOB2, MEPCE, LIF, RGS2, RND3, KLF6, RRP12, and SOCS3) was developed and validated. Survival analysis and ROC curve analysis indicated that the eight LIF-related-gene predictive model had good performance in evaluating patients' prognosis in different subgroups of ccRCC. Conclusion: Our study revealed that LIF plays a carcinogenic role in ccRCC. In addition, we firstly integrated multiple LIF-related genes to set up a risk-predictive model. The model could accurately predict the prognosis of ccRCC, which offers clinical implications for risk stratification, drug screening, and therapeutic decision.
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Cox univariate and LASSO analyses were used to develop risk signatures based on LIF-related genes, and the prognostic model was validated in the ICGC and E-MTAB-1980 databases.
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Cox univariate and LASSO analyses were used to develop risk signatures based on LIF-related genes, and the prognostic model was validated in the ICGC and E-MTAB-1980 databases.
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Next, a prognostic risk prediction model including eight LIF-related genes (TOB2, MEPCE, LIF, RGS2, RND3, KLF6, RRP12, and SOCS3) was developed and validated.
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Next, a prognostic risk prediction model including eight LIF-related genes (TOB2, MEPCE, LIF, RGS2, RND3, KLF6, RRP12, and SOCS3) was developed and validated.
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Next, a prognostic risk prediction model including eight LIF-related genes (TOB2, MEPCE, LIF, RGS2, RND3, KLF6, RRP12, and SOCS3) was developed and validated.
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GSM1300199
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GSM1300200
[139]
GSM1300201
[140]
GSM1300202
[141]
GSM1300203
[142]
GSM1300204
[143]
GSM1300205
sample_count
144
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Gene array analysis of clear cell renal cell carcinoma tissue versus matched normal kidney tissue
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[5] object · 15 fields
id
data:geo:GSE66272
role
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geo-series
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66272
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null
reader_status
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GSE66272
version
null
note
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author/s.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author/s.
access_statement_kind
data_availability_statement
sample_accessions array · 54 items
[0]
GSM1618387
[1]
GSM1618388
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GSM1618389
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GSM1618390
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GSM1618391
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GSM1618392
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GSM1618393
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GSM1618394
[8]
GSM1618395
[9]
GSM1618396
[10]
GSM1618397
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GSM1618398
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GSM1618400
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GSM1618401
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GSM1618402
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GSM1618403
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GSM1618405
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GSM1618406
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GSM1618407
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GSM1618408
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GSM1618410
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GSM1618411
[25]
GSM1618412
[26]
GSM1618413
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GSM1618414
[28]
GSM1618415
[29]
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[30]
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[31]
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GSM1618421
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GSM1618422
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GSM1618423
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GSM1618424
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[44]
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[45]
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[46]
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[47]
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[48]
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[49]
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[50]
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[51]
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[52]
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[53]
GSM1618440
sample_count
54
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Genome-wide analysis of gene expression patterns in human kidney cancer
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
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gaps array · 10 items
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asset:data:geo:E-MTAB-1980 not downloaded
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[3]
asset:data:geo:GSE15641 licence not read
[4]
asset:data:geo:GSE46699 not downloaded
[5]
asset:data:geo:GSE46699 licence not read
[6]
asset:data:geo:GSE53757 not downloaded
[7]
asset:data:geo:GSE53757 licence not read
[8]
asset:data:geo:GSE66272 not downloaded
[9]
asset:data:geo:GSE66272 licence not read
analysis object · 4 fields
state
partial
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id
method-1
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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
0.8
band
high
quote
Cox regression
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id
method-2
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survival_analysis
specific
log_rank_test
label
Survival analysis
dsl_operations array · 1 item
[0]
logrank_test
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
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time_to_event_with_censoring
evidence object · 3 fields
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log-rank
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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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solve_confusion_matrix
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classification_metrics
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parameters object · 0 fields
data_shapes array · 1 item
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reference_standard_and_test
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0.7
band
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quote
ROC curve
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id
method-4
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null
specific
null
label
Cox univariate and LASSO analyses
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missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 0 items
evidence object · 3 fields
score
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Cox univariate and LASSO analyses were used to develop risk signatures based on LIF-related genes, and the prognostic model was validated in the ICGC and E-MTAB-1980 databases.
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gaps array · 1 item
[0]
method.reader_named_unmapped
capability object · 3 fields
state
complete
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[0] object · 6 fields
capability_id
capability:computational_analysis
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Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
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survival_analysis
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statistical_regression
[4]
pca
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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
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true
required_operations array · 1 item
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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
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true
accessions array · 5 items
[0]
GSE15641
[1]
GSE46699
[2]
GSE53757
[3]
GSE66272
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E-MTAB-1980
resolved_accessions array · 5 items
[0]
GSE15641
[1]
GSE46699
[2]
GSE53757
[3]
GSE66272
[4]
E-MTAB-1980
statements array · 1 item
[0]
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author/s.
basis
The paper names GSE15641, GSE46699, GSE53757, GSE66272, E-MTAB-1980 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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dsl_operations array · 1 item
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cox_ph
assets array · 2 items
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source:pmid:35992780
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data:geo:E-MTAB-1980
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run_analysis
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[0]
data:geo:E-MTAB-1980
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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
2026-11-01T18:01:22Z
independence
single_reader
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method
verbatim
availability
verbatim
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5
usage object · 3 fields
prompt_tokens
16051
completion_tokens
2541
cached_tokens
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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pmid:35992780
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paper
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pmid:35992780
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id
source:pmid:35992780
type
manuscript
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PMID 35992780 full text
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id
data:geo:E-MTAB-1980
type
dataset
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GEO E-MTAB-1980
activities array · 3 items
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id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
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id
pmid:35992780
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paper
label
pmid:35992780
[1] object · 3 fields
id
source:pmid:35992780
type
manuscript
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PMID 35992780 full text
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id
data:geo:E-MTAB-1980
type
dataset
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GEO E-MTAB-1980
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agent:corpus-assay-engine
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id
activity-read-35992780
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extraction
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agent:minimax-reader
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activity-resolve-E-MTAB-1980
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accession_resolution
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[0]
data:geo:E-MTAB-1980
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agent:corpus-assay-engine
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agent:corpus-assay-engine
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dsl_catalogue_fingerprint
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capability_table_fingerprint
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lineage object · 4 fields
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[9]
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[0]
oor prognostic effect in ccRCC patients. LIF knockdown can inhibit the migration and invasion of cc
[1]
cRCC patients. Cell lines, cell culture, and transfection The ccRCC cell lines 786-O and ACHN cells we
[2]
hRNA-2, 5′-GGAAGTATAAGCAGATCATCG-3′. The PEI transfection system (Invitrogen) was used for transfectio
[3]
ransfection system (Invitrogen) was used for transfection according to the manufacturer’s guidelines.
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paper_text_order:1570
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paper_text_order:2966
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cox_ph
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35992780", "kind": "science-record", "revision": 4, "content_hash": "sha256:96f3a9072e137905fc3235ba10ec828c295586974cb2966bd50fde69a3bf797f", "created_at": "2026-11-01T18:15:08Z", "updated_at": "2026-11-01T22:07:19Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Elevated expression of LIF predicts a poor prognosis and promotes cell migration and invasion of clear cell renal cell carcinoma.", "doi": "10.3389/fonc.2022.934128", "pmid": "35992780", "authors": ["Wenting Zhong", "Hongxia Liu", "Feng Li", "Youyu Lin", "Yan Ye", "Luyun Xu", "ShengZhao Li", "Hui Chen", "Chengcheng Li", "Yuxuan Lin", "Wei Zhuang", "Yao Lin", "Qingshui Wang"], "journal": "Frontiers in oncology", "year": 2022, "abstract": "Background: Renal cell carcinoma (RCC) is the seventh most common cancer in humans, of which clear cell renal cell carcinoma (ccRCC) accounts for the majority. Recently, although there have been significant breakthroughs in the treatment of ccRCC, the prognosis of targeted therapy is still poor. Leukemia inhibitory factor (LIF) is a pleiotropic protein, which is overexpressed in many cancers and plays a carcinogenic role. In this study, we explored the expression and potential role of LIF in ccRCC.\nMethods: The expression levels and prognostic effects of the LIF gene in ccRCC were detected using TCGA, GEO, ICGC, and ArrayExpress databases. The function of LIF in ccRCC was investigated using a series of cell function approaches. LIF-related genes were identified by weighted gene correlation network analysis (WGCNA). GO and KEGG analyses were performed subsequently. Cox univariate and LASSO analyses were used to develop risk signatures based on LIF-related genes, and the prognostic model was validated in the ICGC and E-MTAB-1980 databases. Then, a nomogram model was constructed for survival prediction and validation of ccRCC patients. To further explore the drug sensitivity between LIF-related genes, we also conducted a drug sensitivity analysis based on the GDSC database.\nResults: The mRNA and protein expression levels of LIF were significantly increased in ccRCC patients. In addition, a high expression of LIF has a poor prognostic effect in ccRCC patients. LIF knockdown can inhibit the migration and invasion of ccRCC cells. By using WGCNA, 97 LIF-related genes in ccRCC were identified. Next, a prognostic risk prediction model including eight LIF-related genes (TOB2, MEPCE, LIF, RGS2, RND3, KLF6, RRP12, and SOCS3) was developed and validated. Survival analysis and ROC curve analysis indicated that the eight LIF-related-gene predictive model had good performance in evaluating patients' prognosis in different subgroups of ccRCC.\nConclusion: Our study revealed that LIF plays a carcinogenic role in ccRCC. In addition, we firstly integrated multiple LIF-related genes to set up a risk-predictive model. The model could accurately predict the prognosis of ccRCC, which offers clinical implications for risk stratification, drug screening, and therapeutic decision.", "claims": [{"id": "claim-method", "statement": "Cox univariate and LASSO analyses were used to develop risk signatures based on LIF-related genes, and the prognostic model was validated in the ICGC and E-MTAB-1980 databases.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35992780", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Cox univariate and LASSO analyses were used to develop risk signatures based on LIF-related genes, and the prognostic model was validated in the ICGC and E-MTAB-1980 databases."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material. 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