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pmid:34761566

The roles of ferroptosis regulatory gene SLC7A11 in renal cell carcinoma: A multi-omics study.

Fangshi Xu · Yibing Guan · Li Xue · Peng Zhang · Mingrui Li · Mei Gao · Tie Chong

Cancer medicine · 2021 doi:10.1002/cam4.4395

Paper

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Experiment

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Data

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Analysis

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pmid:34761566
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title
The roles of ferroptosis regulatory gene SLC7A11 in renal cell carcinoma: A multi-omics study.
doi
10.1002/cam4.4395
pmid
34761566
authors array · 7 items
[0]
Fangshi Xu
[1]
Yibing Guan
[2]
Li Xue
[3]
Peng Zhang
[4]
Mingrui Li
[5]
Mei Gao
[6]
Tie Chong
journal
Cancer medicine
year
2021
abstract
BACKGROUND: The ferroptosis inhibitory gene Solute carrier family 7 member 11 (SLC7A11) provides a new strategy for anticancer treatment. However, its function in renal cell carcinoma (RCC) remains elusive. METHODS: The expression and somatic mutation information of SLC7A11 in RCC samples were determined using The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Gene Expression Omnibus (GEO), Oncomine, and cBioPortal databases. The prognostic value of SLC7A11 was assessed through survival analysis, Receiver operating characteristic curve (ROC) analysis, independent prognostic analysis, clinical subgroup analysis, and nomogram. Its prognostic value was also validated in the ICGC and GSE29607 cohorts. Gene set enrichment analysis (GSEA) was employed to investigate the effects of SLC7A11 on multiple metabolic pathways. The CIBERSORT algorithm and single-sample gene set enrichment analysis (ssGSEA) method were applied to evaluate the effects of SLC7A11 on the tumor immune microenvironment (TIM). SLC7A11's therapeutic correlations were analyzed using the GSE87121, GSE67501, and GSDC datasets. Finally, the biofunctions of SLC7A11 in renal cancer cells and ferroptosis were ascertained by MTT, wound healing, transwell, and western blot assays. RESULTS: Through multiple datasets, SLC7A11 was found to be markedly upregulated in RCC. In terms of prognosis, SLC7A11 overexpression conferred a worse prognosis and was identified as an independent prognostic factor. Its prognostic value was validated in ICGC cohort. Moreover, high SL7CA11 expression could stimulate nucleotides, fatty acids, and amino acid metabolism to meet the proliferative consumption of tumor cells. As for the immune effect, SLC7A11 suppressed antitumor immunity by reducing the abundances of CD8+ T and NK cells. Regarding the therapeutic response, SLC7A11 expression was not correlated with the sensitivities of most chemotherapy and targeted drugs. Finally, SLC7A11 promoted the proliferation, migration, and invasion of renal cancer cells by enhancing GPX4 output, which in turn inhibits ferroptosis. CONCLUSIONS: SLC7A11 not only deeply influences RCC prognosis and TIM, but also promotes RCC progression by inhibiting ferroptosis and inducing metabolic reprogramming. In addition, SLC7A11 weakly affects the therapeutic effect and sensitivities of multiple chemotherapy and targeted drugs.
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Cox univariate and multivariate analyses were successively conducted to identify the independent prognostic factors of RCC.
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sections[5] "Prognostic analyses" paragraph 2
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Cox univariate and multivariate analyses were successively conducted to identify the independent prognostic factors of RCC.
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The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.
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High SLC7A11 expression conferred a poor prognosis, leading to a 3-year survival rate of 62.9%, whereas that of low SLC7A11 expression was 76.2%.
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sections[19] "SLC7A11 provides valuable information for RCC prognostic assessment" paragraph 2
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High SLC7A11 expression conferred a poor prognosis, leading to a 3‐year survival rate of 62.9%, whereas that of low SLC7A11 expression was 76.2% (Figure 3A).
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High SLC7A11 expression conferred a poor prognosis, leading to a 3-year survival rate of 62.9%, whereas that of low SLC7A11 expression was 76.2%.
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GSM1300130
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GSM1300131
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GSM1300133
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GSM1300134
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GSM1300135
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GSM1300136
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GSM1300137
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GSM1300138
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GSM1300139
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GSM1300140
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GSM1300141
[80]
GSM1300142
[81]
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[82]
GSM1300144
[83]
GSM1300145
[84]
GSM1300146
[85]
GSM1300147
[86]
GSM1300148
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GSM1300149
[88]
GSM1300150
[89]
GSM1300151
[90]
GSM1300152
[91]
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[92]
GSM1300154
[93]
GSM1300155
[94]
GSM1300156
[95]
GSM1300157
[96]
GSM1300158
[97]
GSM1300159
[98]
GSM1300160
[99]
GSM1300161
[100]
GSM1300162
[101]
GSM1300163
[102]
GSM1300164
[103]
GSM1300165
[104]
GSM1300166
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GSM1300167
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GSM1300168
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GSM1300169
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GSM1300170
[109]
GSM1300171
[110]
GSM1300172
[111]
GSM1300173
[112]
GSM1300174
[113]
GSM1300175
[114]
GSM1300176
[115]
GSM1300177
[116]
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GSM1300179
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GSM1300180
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GSM1300182
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[123]
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[125]
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[126]
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[130]
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[131]
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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
[7] object · 15 fields
id
data:geo:GSE66271
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=GSE66271
sha256
null
bytes
null
access
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resolved
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null
reader_status
reader_required
identifier
GSE66271
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null
note
The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.
structure object · 15 fields
repository
GEO
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GEO accession URL
access_statement_verbatim
The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.
access_statement_kind
data_availability_statement
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GSM1618415
[1]
GSM1618416
[2]
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GSM1618419
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GSM1618422
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GSM1618424
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[11]
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[12]
GSM1618427
[13]
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[14]
GSM1618429
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GSM1618430
[16]
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[17]
GSM1618432
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GSM1618433
[19]
GSM1618434
[20]
GSM1618435
[21]
GSM1618436
[22]
GSM1618437
[23]
GSM1618438
[24]
GSM1618439
[25]
GSM1618440
sample_count
26
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Genome-wide analysis of gene expression patterns in human kidney cancer [patients with metastasis]
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[8] object · 15 fields
id
data:geo:GSE67501
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=GSE67501
sha256
null
bytes
null
access
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resolved
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null
reader_status
reader_required
identifier
GSE67501
version
null
note
The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.
access_statement_kind
data_availability_statement
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[0]
GSM1648114
[1]
GSM1648115
[2]
GSM1648116
[3]
GSM1648117
[4]
GSM1648118
[5]
GSM1648119
[6]
GSM1648120
[7]
GSM1648121
[8]
GSM1648122
[9]
GSM1648123
[10]
GSM1648124
sample_count
11
group_sizes
null
group_sizes_basis
null
platform
14951
taxon
Homo sapiens
title
Expression data in human renal cell carcinoma samples from patients who did or did not respond to anti-PD-1 (Nivolumab) immunotherapy
resolution_checked_at
2026-11-01T17:30:42Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
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[9] object · 15 fields
id
data:geo:GSE87121
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=GSE87121
sha256
null
bytes
null
access
open
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resolved
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null
reader_status
reader_required
identifier
GSE87121
version
null
note
The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.
access_statement_kind
data_availability_statement
sample_accessions array · 10 items
[0]
GSM2322632
[1]
GSM2322633
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GSM2322634
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GSM2322635
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GSM2322636
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GSM2322637
[6]
GSM2322638
[7]
GSM2322639
[8]
GSM2322640
[9]
GSM2322641
sample_count
10
group_sizes
null
group_sizes_basis
null
platform
5175
taxon
Homo sapiens
title
Sorafenib resistance associated gene expression in renal cell carcinoma
resolution_checked_at
2026-11-01T17:30:42Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 18 items
[0]
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[1]
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[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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[11]
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[13]
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[14]
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[15]
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[16]
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[17]
asset:data:geo:GSE87121 licence not read
analysis object · 4 fields
state
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[0] object · 10 fields
id
method-1
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null
specific
null
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evidence object · 3 fields
score
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band
verbatim
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Cox univariate and multivariate analyses were successively conducted to identify the independent prognostic factors of RCC.
targets array · 0 items
gaps array · 1 item
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method.reader_named_unmapped
capability object · 3 fields
state
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[0] object · 6 fields
capability_id
capability:computational_analysis
label
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assay_families array · 9 items
[0]
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[1]
machine_learning
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survival_analysis
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gwas
candidate
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readiness object · 8 fields
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blocking_axis
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tier
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missing_operations array · 0 items
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The reader quoted the method the paper names (Cox univariate and multivariate analyses), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible.
capability object · 4 fields
tier
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capability:computational_analysis
availability_state
owned
basis
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data object · 6 fields
tier
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accessions array · 9 items
[0]
GSE29609
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GSE66271
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GSE168845
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GSE15641
[5]
GSE105261
[6]
GSE150404
[7]
GSE87121
[8]
GSE67501
resolved_accessions array · 9 items
[0]
GSE29609
[1]
GSE53757
[2]
GSE66271
[3]
GSE168845
[4]
GSE15641
[5]
GSE105261
[6]
GSE150404
[7]
GSE87121
[8]
GSE67501
statements array · 1 item
[0]
The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.
basis
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can_run object · 3 fields
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assets array · 2 items
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source:pmid:34761566
[1]
data:geo:GSE105261
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run_analysis
must_build object · 5 fields
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data:geo:GSE105261
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review object · 5 fields
state
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kind
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MiniMax-M3.1-Flash
provider
minimax
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minimax
read_at
2026-11-01T17:06:59Z
independence
single_reader
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method
verbatim
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prompt_tokens
12425
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3430
cached_tokens
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stages array · 1 item
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pmid:34761566
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paper
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pmid:34761566
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source:pmid:34761566
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manuscript
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PMID 34761566 full text
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[7]
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[11]
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[13]
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[14]
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[15]
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[16]
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[17]
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er cells and ferroptosis were ascertained by MTT, wound healing, transwell, and western blot
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tained by MTT, wound healing, transwell, and western blot assays. RESULTS: Through multiple datasets,
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[0]
MATERIALS AND METHODS Cell culture and transfection The normal kidney tubular epithelial cell li
[1]
gy Company. Lipofectamine™ 2000 was used for transfection (Thermo Fisher Scientific). Statistical anal
[2]
O2, and 95% humidity. Small interfering RNA (siRNA) for SLC7A11 silencing was designed and synt
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assay:3
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ence and Technology Company. HK‐2 cells were cultured in minimum essential medium containing 10% feta
[1]
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34761566", "kind": "science-record", "revision": 3, "content_hash": "sha256:245395c5cf23089fe98a41225e2403e8f2e574078149905fe8fab2737e8a96e7", "created_at": "2026-11-01T17:36:27Z", "updated_at": "2026-11-01T21:26:35Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The roles of ferroptosis regulatory gene SLC7A11 in renal cell carcinoma: A multi-omics study.", "doi": "10.1002/cam4.4395", "pmid": "34761566", "authors": ["Fangshi Xu", "Yibing Guan", "Li Xue", "Peng Zhang", "Mingrui Li", "Mei Gao", "Tie Chong"], "journal": "Cancer medicine", "year": 2021, "abstract": "BACKGROUND: The ferroptosis inhibitory gene Solute carrier family 7 member 11 (SLC7A11) provides a new strategy for anticancer treatment. However, its function in renal cell carcinoma (RCC) remains elusive.\nMETHODS: The expression and somatic mutation information of SLC7A11 in RCC samples were determined using The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Gene Expression Omnibus (GEO), Oncomine, and cBioPortal databases. The prognostic value of SLC7A11 was assessed through survival analysis, Receiver operating characteristic curve (ROC) analysis, independent prognostic analysis, clinical subgroup analysis, and nomogram. Its prognostic value was also validated in the ICGC and GSE29607 cohorts. Gene set enrichment analysis (GSEA) was employed to investigate the effects of SLC7A11 on multiple metabolic pathways. The CIBERSORT algorithm and single-sample gene set enrichment analysis (ssGSEA) method were applied to evaluate the effects of SLC7A11 on the tumor immune microenvironment (TIM). SLC7A11's therapeutic correlations were analyzed using the GSE87121, GSE67501, and GSDC datasets. Finally, the biofunctions of SLC7A11 in renal cancer cells and ferroptosis were ascertained by MTT, wound healing, transwell, and western blot assays.\nRESULTS: Through multiple datasets, SLC7A11 was found to be markedly upregulated in RCC. In terms of prognosis, SLC7A11 overexpression conferred a worse prognosis and was identified as an independent prognostic factor. Its prognostic value was validated in ICGC cohort. Moreover, high SL7CA11 expression could stimulate nucleotides, fatty acids, and amino acid metabolism to meet the proliferative consumption of tumor cells. As for the immune effect, SLC7A11 suppressed antitumor immunity by reducing the abundances of CD8+ T and NK cells. Regarding the therapeutic response, SLC7A11 expression was not correlated with the sensitivities of most chemotherapy and targeted drugs. Finally, SLC7A11 promoted the proliferation, migration, and invasion of renal cancer cells by enhancing GPX4 output, which in turn inhibits ferroptosis.\nCONCLUSIONS: SLC7A11 not only deeply influences RCC prognosis and TIM, but also promotes RCC progression by inhibiting ferroptosis and inducing metabolic reprogramming. 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RESULTS: Through multiple datasets,"], "order_basis": "paper_text_order:1311", "id": "assay:2"}, {"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": ["MATERIALS AND METHODS Cell culture and transfection The normal kidney tubular epithelial cell li", "gy Company. Lipofectamine™ 2000 was used for transfection (Thermo Fisher Scientific). Statistical anal", "O2, and 95% humidity. Small interfering RNA (siRNA) for SLC7A11 silencing was designed and synt"], "order_basis": "paper_text_order:2500", "id": "assay:3"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ence and Technology Company. HK‐2 cells were cultured in minimum essential medium containing 10% feta", "llin/streptomycin. 786‐O and A498 cells were cultured in RPMI‐1640 medium (Roswell Park Memorial Inst"], "order_basis": "paper_text_order:2683", "id": "assay:4"}]}