Corpus Engine Towards a reproducible .science file.
← All .science files

pmid:35999846

A cholesterogenic gene signature for predicting the prognosis of young breast cancer patients.

Xiaoping Li · Chaorong Zhou · Chaoran Qiu · Weiwen Li · Qihe Yu · Hui Huang · Yiwen Zhang · Xin Zhang · Liangliang Ren · Xin Huang · Qinghua Zhou

PeerJ · 2022 doi:10.7717/peerj.13922

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

Execution evidence has not yet been added to this .science file. Explore its methods, data and open questions to plan the next step.
Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
id
pmid:35999846
kind
science-record
content_hash
sha256:4ba0f32c86b75a051b63e5906a88e86de4141b38999dbf195678db1266f4187d
schema
https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json
created_at
2026-11-01T18:15:09Z
updated_at
2026-11-01T22:07:20Z
generator object · 2 fields
name
corpus-assay-engine
run_id
reading-sci-2026-11-01
paper object · 10 fields
state
complete
title
A cholesterogenic gene signature for predicting the prognosis of young breast cancer patients.
doi
10.7717/peerj.13922
pmid
35999846
authors array · 11 items
[0]
Xiaoping Li
[1]
Chaorong Zhou
[2]
Chaoran Qiu
[3]
Weiwen Li
[4]
Qihe Yu
[5]
Hui Huang
[6]
Yiwen Zhang
[7]
Xin Zhang
[8]
Liangliang Ren
[9]
Xin Huang
[10]
Qinghua Zhou
journal
PeerJ
year
2022
abstract
Purpose: We aimed to establish a cholesterogenic gene signature to predict the prognosis of young breast cancer (BC) patients and then verified it using cell line experiments. Methods: In the bioinformatic section, transcriptional data and corresponding clinical data of young BC patients (age ≤ 45 years) were downloaded from The Cancer Genome Atlas (TCGA) database for training set. Differentially expressed genes (DEGs) were compared between tumour tissue (n = 183) and normal tissue (n = 30). By using univariate Cox regression and multi COX regression, a five-cholesterogenic-gene signature was established to predict prognosis. Subgroup analysis and external validations of GSE131769 from the Gene Expression Omnibus (GEO) were performed to verify the signature. Subsequently, in experiment part, cell experiments were performed to further verify the biological roles of the five cholesterogenic genes in BC. Results: In the bioinformatic section, a total of 97 upregulated genes and 124 downregulated cholesterogenic genes were screened as DEGs in the TCGA for training the model. A risk scoring signature contained five cholesterogenic genes (risk score = -1.169 × GRAMD1C -0.992 × NFKBIA + 0.432 × INHBA + 0.261 × CD24 -0.839 × ACSS2) was established, which could differentiate the prognosis of young BC patients between high-risk and low-risk group (<0.001). The prediction value of chelesterogenic gene signature in excellent with AUC was 0.810 in TCGA dataset. Then the prediction value of the signature was verified in GSE131769 with P = 0.033. In experiment part, although the downregulation of CD24, GRAMD1C and ACSS2 did not significantly affect cell viability, NFKBIA downregulation promoted the viability, colony forming ability and invasion capability of BC cells, while INHBA downregulation had the opposite effects. Conclusion: The five-cholesterogenic-gene signature had independent prognostic value and robust reliability in predicting the prognosis of young BC patients. The cell experiment results suggested that NFKBIA played a protective role, while INHBA played the pro-cancer role in breast cancer.
claims array · 3 items
[0] object · 6 fields
id
claim-method
statement
By using univariate Cox regression and multi COX regression, a five-cholesterogenic-gene signature was established to predict prognosis.
kind
methodological
target
null
evidence array · 1 item
[0] object · 3 fields
asset
source:pmid:35999846
locator
sections[0] "Abstract" paragraph 2
quote
By using univariate Cox regression and multi COX regression, a five-cholesterogenic-gene signature was established to predict prognosis.
state
complete
[1] object · 6 fields
id
claim-data-access
statement
The raw data are available in the Supplementary File.
kind
methodological
target
null
evidence array · 1 item
[0] object · 3 fields
asset
source:pmid:35999846
locator
sections[24] "Additional Information and Declarations" paragraph 5
quote
The raw data are available in the Supplementary File.
state
complete
[2] object · 6 fields
id
claim-target-result
statement
The prediction value of chelesterogenic gene signature in excellent with AUC was 0.810 in TCGA dataset.
kind
quantitative
target object · 4 fields
value
0.81
unit
auc
tolerance
null
source
The prediction value of chelesterogenic gene signature in excellent with AUC was 0.810 in TCGA dataset.
evidence array · 1 item
[0] object · 3 fields
asset
source:pmid:35999846
locator
sections[0] "Abstract" paragraph 3
quote
The prediction value of chelesterogenic gene signature in excellent with AUC was 0.810 in TCGA dataset.
state
complete
gaps array · 0 items
experiment object · 8 fields
state
complete
objective
The prediction value of chelesterogenic gene signature in excellent with AUC was 0.810 in TCGA dataset.
steps array · 3 items
[0] object · 13 fields
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.
parameters object · 0 fields
inputs array · 1 item
[0]
source:pmid:35999846
outputs array · 1 item
[0]
the published estimate and its evidence
instruments array · 0 items
reagents array · 0 items
[1] object · 13 fields
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.
parameters object · 0 fields
inputs array · 1 item
[0]
data:geo:GSE131769
outputs array · 1 item
[0]
the source data with its repository provenance
instruments array · 0 items
reagents array · 0 items
[2] object · 13 fields
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.
parameters object · 0 fields
inputs array · 1 item
[0]
data:geo:GSE131769
outputs array · 1 item
[0]
the replicated result and its comparison
instruments array · 0 items
reagents array · 0 items
materials array · 0 items
instruments array · 0 items
reagents array · 0 items
conditions object · 0 fields
gaps array · 0 items
data object · 3 fields
state
partial
assets array · 2 items
[0] object · 15 fields
id
source:pmid:35999846
role
manuscript
format
xml
media_type
application/xml
uri
https://doi.org/10.7717/peerj.13922
sha256
sha256:415e5d0e17a6ff2f71597bf5c409e8521acf98d7846a93775c7ba9db0048daa8
bytes
32552
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
10.7717/peerj.13922
version
null
note
Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.
structure object · 4 fields
pmcid
PMC9393010
source
europe_pmc_fulltext
coverage
whole_body_without_references
text_hash_scope
rendered_section_body
[1] object · 15 fields
id
data:geo:GSE131769
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=GSE131769
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE131769
version
null
note
The raw data are available in the Supplementary File.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The raw data are available in the Supplementary File.
access_statement_kind
data_availability_statement
sample_accessions array · 301 items
[0]
GSM3818017
[1]
GSM3818018
[2]
GSM3818019
[3]
GSM3818020
[4]
GSM3818021
[5]
GSM3818022
[6]
GSM3818023
[7]
GSM3818024
[8]
GSM3818025
[9]
GSM3818026
[10]
GSM3818027
[11]
GSM3818028
[12]
GSM3818029
[13]
GSM3818030
[14]
GSM3818031
[15]
GSM3818032
[16]
GSM3818033
[17]
GSM3818034
[18]
GSM3818035
[19]
GSM3818036
[20]
GSM3818037
[21]
GSM3818038
[22]
GSM3818039
[23]
GSM3818040
[24]
GSM3818041
[25]
GSM3818042
[26]
GSM3818043
[27]
GSM3818044
[28]
GSM3818045
[29]
GSM3818046
[30]
GSM3818047
[31]
GSM3818048
[32]
GSM3818049
[33]
GSM3818050
[34]
GSM3818051
[35]
GSM3818052
[36]
GSM3818053
[37]
GSM3818054
[38]
GSM3818055
[39]
GSM3818056
[40]
GSM3818057
[41]
GSM3818058
[42]
GSM3818059
[43]
GSM3818060
[44]
GSM3818061
[45]
GSM3818062
[46]
GSM3818063
[47]
GSM3818064
[48]
GSM3818065
[49]
GSM3818066
[50]
GSM3818067
[51]
GSM3818068
[52]
GSM3818069
[53]
GSM3818070
[54]
GSM3818071
[55]
GSM3818072
[56]
GSM3818073
[57]
GSM3818074
[58]
GSM3818075
[59]
GSM3818076
[60]
GSM3818077
[61]
GSM3818078
[62]
GSM3818079
[63]
GSM3818080
[64]
GSM3818081
[65]
GSM3818082
[66]
GSM3818083
[67]
GSM3818084
[68]
GSM3818085
[69]
GSM3818086
[70]
GSM3818087
[71]
GSM3818088
[72]
GSM3818089
[73]
GSM3818090
[74]
GSM3818091
[75]
GSM3818092
[76]
GSM3818093
[77]
GSM3818094
[78]
GSM3818095
[79]
GSM3818096
[80]
GSM3818097
[81]
GSM3818098
[82]
GSM3818099
[83]
GSM3818100
[84]
GSM3818101
[85]
GSM3818102
[86]
GSM3818103
[87]
GSM3818104
[88]
GSM3818105
[89]
GSM3818106
[90]
GSM3818107
[91]
GSM3818108
[92]
GSM3818109
[93]
GSM3818110
[94]
GSM3818111
[95]
GSM3818112
[96]
GSM3818113
[97]
GSM3818114
[98]
GSM3818115
[99]
GSM3818116
[100]
GSM3818117
[101]
GSM3818118
[102]
GSM3818119
[103]
GSM3818120
[104]
GSM3818121
[105]
GSM3818122
[106]
GSM3818123
[107]
GSM3818124
[108]
GSM3818125
[109]
GSM3818126
[110]
GSM3818127
[111]
GSM3818128
[112]
GSM3818129
[113]
GSM3818130
[114]
GSM3818131
[115]
GSM3818132
[116]
GSM3818133
[117]
GSM3818134
[118]
GSM3818135
[119]
GSM3818136
[120]
GSM3818137
[121]
GSM3818138
[122]
GSM3818139
[123]
GSM3818140
[124]
GSM3818141
[125]
GSM3818142
[126]
GSM3818143
[127]
GSM3818144
[128]
GSM3818145
[129]
GSM3818146
[130]
GSM3818147
[131]
GSM3818148
[132]
GSM3818149
[133]
GSM3818150
[134]
GSM3818151
[135]
GSM3818152
[136]
GSM3818153
[137]
GSM3818154
[138]
GSM3818155
[139]
GSM3818156
[140]
GSM3818157
[141]
GSM3818158
[142]
GSM3818159
[143]
GSM3818160
[144]
GSM3818161
[145]
GSM3818162
[146]
GSM3818163
[147]
GSM3818164
[148]
GSM3818165
[149]
GSM3818166
[150]
GSM3818167
[151]
GSM3818168
[152]
GSM3818169
[153]
GSM3818170
[154]
GSM3818171
[155]
GSM3818172
[156]
GSM3818173
[157]
GSM3818174
[158]
GSM3818175
[159]
GSM3818176
[160]
GSM3818177
[161]
GSM3818178
[162]
GSM3818179
[163]
GSM3818180
[164]
GSM3818181
[165]
GSM3818182
[166]
GSM3818183
[167]
GSM3818184
[168]
GSM3818185
[169]
GSM3818186
[170]
GSM3818187
[171]
GSM3818188
[172]
GSM3818189
[173]
GSM3818190
[174]
GSM3818191
[175]
GSM3818192
[176]
GSM3818193
[177]
GSM3818194
[178]
GSM3818195
[179]
GSM3818196
[180]
GSM3818197
[181]
GSM3818198
[182]
GSM3818199
[183]
GSM3818200
[184]
GSM3818201
[185]
GSM3818202
[186]
GSM3818203
[187]
GSM3818204
[188]
GSM3818205
[189]
GSM3818206
[190]
GSM3818207
[191]
GSM3818208
[192]
GSM3818209
[193]
GSM3818210
[194]
GSM3818211
[195]
GSM3818212
[196]
GSM3818213
[197]
GSM3818214
[198]
GSM3818215
[199]
GSM3818216
[200]
GSM3818217
[201]
GSM3818218
[202]
GSM3818219
[203]
GSM3818220
[204]
GSM3818221
[205]
GSM3818222
[206]
GSM3818223
[207]
GSM3818224
[208]
GSM3818225
[209]
GSM3818226
[210]
GSM3818227
[211]
GSM3818228
[212]
GSM3818229
[213]
GSM3818230
[214]
GSM3818231
[215]
GSM3818232
[216]
GSM3818233
[217]
GSM3818234
[218]
GSM3818235
[219]
GSM3818236
[220]
GSM3818237
[221]
GSM3818238
[222]
GSM3818239
[223]
GSM3818240
[224]
GSM3818241
[225]
GSM3818242
[226]
GSM3818243
[227]
GSM3818244
[228]
GSM3818245
[229]
GSM3818246
[230]
GSM3818247
[231]
GSM3818248
[232]
GSM3818249
[233]
GSM3818250
[234]
GSM3818251
[235]
GSM3818252
[236]
GSM3818253
[237]
GSM3818254
[238]
GSM3818255
[239]
GSM3818256
[240]
GSM3818257
[241]
GSM3818258
[242]
GSM3818259
[243]
GSM3818260
[244]
GSM3818261
[245]
GSM3818262
[246]
GSM3818263
[247]
GSM3818264
[248]
GSM3818265
[249]
GSM3818266
[250]
GSM3818267
[251]
GSM3818268
[252]
GSM3818269
[253]
GSM3818270
[254]
GSM3818271
[255]
GSM3818272
[256]
GSM3818273
[257]
GSM3818274
[258]
GSM3818275
[259]
GSM3818276
[260]
GSM3818277
[261]
GSM3818278
[262]
GSM3818279
[263]
GSM3818280
[264]
GSM3818281
[265]
GSM3818282
[266]
GSM3818283
[267]
GSM3818284
[268]
GSM3818285
[269]
GSM3818286
[270]
GSM3818287
[271]
GSM3818288
[272]
GSM3818289
[273]
GSM3818290
[274]
GSM3818291
[275]
GSM3818292
[276]
GSM3818293
[277]
GSM3818294
[278]
GSM3818295
[279]
GSM3818296
[280]
GSM3818297
[281]
GSM3818298
[282]
GSM3818299
[283]
GSM3818300
[284]
GSM3818301
[285]
GSM3818302
[286]
GSM3818303
[287]
GSM3818304
[288]
GSM3818305
[289]
GSM3818306
[290]
GSM3818307
[291]
GSM3818308
[292]
GSM3818309
[293]
GSM3818310
[294]
GSM3818311
[295]
GSM3818312
[296]
GSM3818313
[297]
GSM3818314
[298]
GSM3818315
[299]
GSM3818316
[300]
GSM3818317
sample_count
301
group_sizes
null
group_sizes_basis
null
platform
6947
taxon
Homo sapiens
title
Genomic signature of the standardized uptake value in 18F-fluorodeoxyglucose positron emission tomography in breast cancer
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 2 items
[0]
asset:data:geo:GSE131769 not downloaded
[1]
asset:data:geo:GSE131769 licence not read
analysis object · 4 fields
state
partial
methods array · 2 items
[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
By using univariate Cox regression and multi COX regression, a five-cholesterogenic-gene signature was established to predict prognosis.
[1] object · 10 fields
id
method-2
family
group_comparison
specific
anova
label
Group comparison
dsl_operations array · 4 items
[0]
group_summary
[1]
welch_t
[2]
bootstrap_mean_difference
[3]
group_comparison_anova
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
two_or_more_groups_continuous
evidence object · 3 fields
score
0.8
band
high
quote
analysis of variance
targets array · 1 item
[0] object · 8 fields
id
target-published-estimate
claim_id
claim-target-result
operation
bootstrap_mean_difference
unit
auc
tolerance
null
state
complete
note
The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none.
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]
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 · 1 item
[0]
GSE131769
resolved_accessions array · 1 item
[0]
GSE131769
statements array · 1 item
[0]
The raw data are available in the Supplementary File.
basis
The paper names GSE131769 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]
cox_ph
assets array · 2 items
[0]
source:pmid:35999846
[1]
data:geo:GSE131769
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:GSE131769
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
2026-11-01T18:01:30Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
9448
completion_tokens
2021
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:35999846
type
paper
label
pmid:35999846
[1] object · 3 fields
id
source:pmid:35999846
type
manuscript
label
PMID 35999846 full text
[2] object · 3 fields
id
data:geo:GSE131769
type
dataset
label
GEO GSE131769
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:35999846
type
paper
label
pmid:35999846
[1] object · 3 fields
id
source:pmid:35999846
type
manuscript
label
PMID 35999846 full text
[2] object · 3 fields
id
data:geo:GSE131769
type
dataset
label
GEO GSE131769
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-35999846
type
extraction
used array · 1 item
[0]
source:pmid:35999846
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE131769
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE131769
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:35999846
parent_hash
sha256:6dc46e276231a333fa498e400ee16100ed785f6234b2ec403a493fde33042e14
fork_of
null
gaps array · 7 items
[0]
asset:data:geo:GSE131769 licence not read
[1]
asset:data:geo:GSE131769 not downloaded
[2]
execution.not_run
[3]
method.reader_differs_from_extractor
[4]
review.human_critique
[5]
review.independent_reader
[6]
review.machine_critique
assays array · 3 items
[0] object · 11 fields
role
data_generation
definition_id
transfection
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 2 items
[0]
Experimental part Cell culture and transient transfection The human BC cell lines MDA-MB-231 and MCF7
[1]
of 7 × 104 cells/500 µL per well. Transient transfection of the plasmids was performed using Lipofect
order_basis
paper_text_order:2245
id
assay:1
[1] 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
0.99
evidence array · 2 items
[0]
llection (Manassas, VA, USA). The cells were cultured in Dulbecco’s modified Eagle medium (DMEM, Gibc
[1]
ction The human BC cell lines MDA-MB-231 and MCF7 were obtained from the American Type Culture
order_basis
paper_text_order:2297
id
assay:2
[2] object · 11 fields
role
analysis
definition_id
survival_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
cox_ph
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
By using univariate Cox regression and multi COX regression, a five-cholesterogenic-gene signature was established to predict prognosis.
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:35999846", "kind": "science-record", "revision": 4, "content_hash": "sha256:4ba0f32c86b75a051b63e5906a88e86de4141b38999dbf195678db1266f4187d", "created_at": "2026-11-01T18:15:09Z", "updated_at": "2026-11-01T22:07:20Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A cholesterogenic gene signature for predicting the prognosis of young breast cancer patients.", "doi": "10.7717/peerj.13922", "pmid": "35999846", "authors": ["Xiaoping Li", "Chaorong Zhou", "Chaoran Qiu", "Weiwen Li", "Qihe Yu", "Hui Huang", "Yiwen Zhang", "Xin Zhang", "Liangliang Ren", "Xin Huang", "Qinghua Zhou"], "journal": "PeerJ", "year": 2022, "abstract": "Purpose: We aimed to establish a cholesterogenic gene signature to predict the prognosis of young breast cancer (BC) patients and then verified it using cell line experiments.\nMethods: In the bioinformatic section, transcriptional data and corresponding clinical data of young BC patients (age ≤ 45 years) were downloaded from The Cancer Genome Atlas (TCGA) database for training set. Differentially expressed genes (DEGs) were compared between tumour tissue (n = 183) and normal tissue (n = 30). By using univariate Cox regression and multi COX regression, a five-cholesterogenic-gene signature was established to predict prognosis. Subgroup analysis and external validations of GSE131769 from the Gene Expression Omnibus (GEO) were performed to verify the signature. Subsequently, in experiment part, cell experiments were performed to further verify the biological roles of the five cholesterogenic genes in BC.\nResults: In the bioinformatic section, a total of 97 upregulated genes and 124 downregulated cholesterogenic genes were screened as DEGs in the TCGA for training the model. A risk scoring signature contained five cholesterogenic genes (risk score = -1.169 × GRAMD1C -0.992 × NFKBIA + 0.432 × INHBA + 0.261 × CD24 -0.839 × ACSS2) was established, which could differentiate the prognosis of young BC patients between high-risk and low-risk group (<0.001). The prediction value of chelesterogenic gene signature in excellent with AUC was 0.810 in TCGA dataset. Then the prediction value of the signature was verified in GSE131769 with P = 0.033. In experiment part, although the downregulation of CD24, GRAMD1C and ACSS2 did not significantly affect cell viability, NFKBIA downregulation promoted the viability, colony forming ability and invasion capability of BC cells, while INHBA downregulation had the opposite effects.\nConclusion: The five-cholesterogenic-gene signature had independent prognostic value and robust reliability in predicting the prognosis of young BC patients. The cell experiment results suggested that NFKBIA played a protective role, while INHBA played the pro-cancer role in breast cancer.", "claims": [{"id": "claim-method", "statement": "By using univariate Cox regression and multi COX regression, a five-cholesterogenic-gene signature was established to predict prognosis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35999846", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "By using univariate Cox regression and multi COX regression, a five-cholesterogenic-gene signature was established to predict prognosis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data are available in the Supplementary File.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35999846", "locator": "sections[24] \"Additional Information and Declarations\" paragraph 5", "quote": "The raw data are available in the Supplementary File."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The prediction value of chelesterogenic gene signature in excellent with AUC was 0.810 in TCGA dataset.", "kind": "quantitative", "target": {"value": 0.81, "unit": "auc", "tolerance": null, "source": "The prediction value of chelesterogenic gene signature in excellent with AUC was 0.810 in TCGA dataset."}, "evidence": [{"asset": "source:pmid:35999846", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The prediction value of chelesterogenic gene signature in excellent with AUC was 0.810 in TCGA dataset."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The prediction value of chelesterogenic gene signature in excellent with AUC was 0.810 in TCGA dataset.", "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:35999846"], "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:GSE131769"], "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:GSE131769"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35999846", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.13922", "sha256": "sha256:415e5d0e17a6ff2f71597bf5c409e8521acf98d7846a93775c7ba9db0048daa8", "bytes": 32552, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7717/peerj.13922", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9393010", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE131769", "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=GSE131769", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE131769", "version": null, "note": "The raw data are available in the Supplementary File.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The raw data are available in the Supplementary File.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3818017", "GSM3818018", "GSM3818019", "GSM3818020", "GSM3818021", "GSM3818022", "GSM3818023", "GSM3818024", "GSM3818025", "GSM3818026", "GSM3818027", "GSM3818028", "GSM3818029", "GSM3818030", "GSM3818031", "GSM3818032", "GSM3818033", "GSM3818034", "GSM3818035", "GSM3818036", "GSM3818037", "GSM3818038", "GSM3818039", "GSM3818040", "GSM3818041", "GSM3818042", "GSM3818043", "GSM3818044", "GSM3818045", "GSM3818046", "GSM3818047", "GSM3818048", "GSM3818049", "GSM3818050", "GSM3818051", "GSM3818052", "GSM3818053", "GSM3818054", "GSM3818055", "GSM3818056", "GSM3818057", "GSM3818058", "GSM3818059", "GSM3818060", "GSM3818061", "GSM3818062", "GSM3818063", "GSM3818064", "GSM3818065", "GSM3818066", "GSM3818067", "GSM3818068", "GSM3818069", "GSM3818070", "GSM3818071", "GSM3818072", "GSM3818073", "GSM3818074", "GSM3818075", "GSM3818076", "GSM3818077", "GSM3818078", "GSM3818079", "GSM3818080", "GSM3818081", "GSM3818082", "GSM3818083", "GSM3818084", "GSM3818085", "GSM3818086", "GSM3818087", "GSM3818088", "GSM3818089", "GSM3818090", "GSM3818091", "GSM3818092", "GSM3818093", "GSM3818094", "GSM3818095", "GSM3818096", "GSM3818097", "GSM3818098", "GSM3818099", "GSM3818100", "GSM3818101", "GSM3818102", "GSM3818103", "GSM3818104", "GSM3818105", "GSM3818106", "GSM3818107", "GSM3818108", "GSM3818109", "GSM3818110", "GSM3818111", "GSM3818112", "GSM3818113", "GSM3818114", "GSM3818115", "GSM3818116", "GSM3818117", "GSM3818118", "GSM3818119", "GSM3818120", "GSM3818121", "GSM3818122", "GSM3818123", "GSM3818124", "GSM3818125", "GSM3818126", "GSM3818127", "GSM3818128", "GSM3818129", "GSM3818130", "GSM3818131", "GSM3818132", "GSM3818133", "GSM3818134", "GSM3818135", "GSM3818136", "GSM3818137", "GSM3818138", "GSM3818139", "GSM3818140", "GSM3818141", "GSM3818142", "GSM3818143", "GSM3818144", "GSM3818145", "GSM3818146", "GSM3818147", "GSM3818148", "GSM3818149", "GSM3818150", "GSM3818151", "GSM3818152", "GSM3818153", "GSM3818154", "GSM3818155", "GSM3818156", "GSM3818157", "GSM3818158", "GSM3818159", "GSM3818160", "GSM3818161", "GSM3818162", "GSM3818163", "GSM3818164", "GSM3818165", "GSM3818166", "GSM3818167", "GSM3818168", "GSM3818169", "GSM3818170", "GSM3818171", "GSM3818172", "GSM3818173", "GSM3818174", "GSM3818175", "GSM3818176", "GSM3818177", "GSM3818178", "GSM3818179", "GSM3818180", "GSM3818181", "GSM3818182", "GSM3818183", "GSM3818184", "GSM3818185", "GSM3818186", "GSM3818187", "GSM3818188", "GSM3818189", "GSM3818190", "GSM3818191", "GSM3818192", "GSM3818193", "GSM3818194", "GSM3818195", "GSM3818196", "GSM3818197", "GSM3818198", "GSM3818199", "GSM3818200", "GSM3818201", "GSM3818202", "GSM3818203", "GSM3818204", "GSM3818205", "GSM3818206", "GSM3818207", "GSM3818208", "GSM3818209", "GSM3818210", "GSM3818211", "GSM3818212", "GSM3818213", "GSM3818214", "GSM3818215", "GSM3818216", "GSM3818217", "GSM3818218", "GSM3818219", "GSM3818220", "GSM3818221", "GSM3818222", "GSM3818223", "GSM3818224", "GSM3818225", "GSM3818226", "GSM3818227", "GSM3818228", "GSM3818229", "GSM3818230", "GSM3818231", "GSM3818232", "GSM3818233", "GSM3818234", "GSM3818235", "GSM3818236", "GSM3818237", "GSM3818238", "GSM3818239", "GSM3818240", "GSM3818241", "GSM3818242", "GSM3818243", "GSM3818244", "GSM3818245", "GSM3818246", "GSM3818247", "GSM3818248", "GSM3818249", "GSM3818250", "GSM3818251", "GSM3818252", "GSM3818253", "GSM3818254", "GSM3818255", "GSM3818256", "GSM3818257", "GSM3818258", "GSM3818259", "GSM3818260", "GSM3818261", "GSM3818262", "GSM3818263", "GSM3818264", "GSM3818265", "GSM3818266", "GSM3818267", "GSM3818268", "GSM3818269", "GSM3818270", "GSM3818271", "GSM3818272", "GSM3818273", "GSM3818274", "GSM3818275", "GSM3818276", "GSM3818277", "GSM3818278", "GSM3818279", "GSM3818280", "GSM3818281", "GSM3818282", "GSM3818283", "GSM3818284", "GSM3818285", "GSM3818286", "GSM3818287", "GSM3818288", "GSM3818289", "GSM3818290", "GSM3818291", "GSM3818292", "GSM3818293", "GSM3818294", "GSM3818295", "GSM3818296", "GSM3818297", "GSM3818298", "GSM3818299", "GSM3818300", "GSM3818301", "GSM3818302", "GSM3818303", "GSM3818304", "GSM3818305", "GSM3818306", "GSM3818307", "GSM3818308", "GSM3818309", "GSM3818310", "GSM3818311", "GSM3818312", "GSM3818313", "GSM3818314", "GSM3818315", "GSM3818316", "GSM3818317"], "sample_count": 301, "group_sizes": null, "group_sizes_basis": null, "platform": "6947", "taxon": "Homo sapiens", "title": "Genomic signature of the standardized uptake value in 18F-fluorodeoxyglucose positron emission tomography in breast cancer", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE131769 not downloaded", "asset:data:geo:GSE131769 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "By using univariate Cox regression and multi COX regression, a five-cholesterogenic-gene signature was established to predict prognosis."}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "analysis of variance"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "bootstrap_mean_difference", "expected_value": 0.81, "unit": "auc", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "capability": {"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": {"tier": "R1", "reachable": true, "accessions": ["GSE131769"], "resolved_accessions": ["GSE131769"], "statements": ["The raw data are available in the Supplementary File."], "basis": "The paper names GSE131769 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:35999846", "data:geo:GSE131769"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE131769"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:01:30Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9448, "completion_tokens": 2021, "cached_tokens": 128}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:35999846", "type": "paper", "label": "pmid:35999846"}, {"id": "source:pmid:35999846", "type": "manuscript", "label": "PMID 35999846 full text"}, {"id": "data:geo:GSE131769", "type": "dataset", "label": "GEO GSE131769"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35999846", "type": "paper", "label": "pmid:35999846"}, {"id": "source:pmid:35999846", "type": "manuscript", "label": "PMID 35999846 full text"}, {"id": "data:geo:GSE131769", "type": "dataset", "label": "GEO GSE131769"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35999846", "type": "extraction", "used": ["source:pmid:35999846"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE131769", "type": "accession_resolution", "used": ["data:geo:GSE131769"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"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": {"parent_id": "pmid:35999846", "parent_hash": "sha256:6dc46e276231a333fa498e400ee16100ed785f6234b2ec403a493fde33042e14", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE131769 licence not read", "asset:data:geo:GSE131769 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["Experimental part Cell culture and transient transfection The human BC cell lines MDA-MB-231 and MCF7", "of 7 × 104 cells/500 µL per well. Transient transfection of the plasmids was performed using Lipofect"], "order_basis": "paper_text_order:2245", "id": "assay:1"}, {"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": ["llection (Manassas, VA, USA). The cells were cultured in Dulbecco’s modified Eagle medium (DMEM, Gibc", "ction The human BC cell lines MDA-MB-231 and MCF7 were obtained from the American Type Culture"], "order_basis": "paper_text_order:2297", "id": "assay:2"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["By using univariate Cox regression and multi COX regression, a five-cholesterogenic-gene signature was established to predict prognosis."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}