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pmid:39540710

Predictive Prognostic Model for Hepatocellular Carcinoma Based on Seven Genes Participating in Arachidonic Acid Metabolism.

Xinyu Gu · Jing Wang · Jun Guan · Guojun Li · Xiao Ma · Yanli Ren · Shanshan Wu · Chao Chen · Haihong Zhu

Cancer medicine · 2024 doi:10.1002/cam4.70284

Paper

complete

Experiment

complete

Data

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Analysis

complete

Execution

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title
Predictive Prognostic Model for Hepatocellular Carcinoma Based on Seven Genes Participating in Arachidonic Acid Metabolism.
doi
10.1002/cam4.70284
pmid
39540710
authors array · 9 items
[0]
Xinyu Gu
[1]
Jing Wang
[2]
Jun Guan
[3]
Guojun Li
[4]
Xiao Ma
[5]
Yanli Ren
[6]
Shanshan Wu
[7]
Chao Chen
[8]
Haihong Zhu
journal
Cancer medicine
year
2024
abstract
BACKGROUND: The occult onset and rapid progression of hepatocellular carcinoma (HCC) lead to an unsatisfactory overall survival (OS) rate. Established prognostic predictive models based on tumor-node-metastasis staging and predictive factors do not report satisfactory predictive efficacy. Arachidonic acid plays pivotal roles in biological processes including inflammation, regeneration, immune modulation, and tumorigenesis. We, therefore, constructed a prognostic predictive model based on seven genes linked to arachidonic acid metabolism, using samples of HCC patients from databases to analyze the genomic profiles. We also assessed the predictive stability of the constructed model. METHODS: Sample data of 365 patients diagnosed with HCC were extracted from The Cancer Genome Atlas (TCGA, training set) and HCCDB18, GSE14520, and GSE76427 databases (validation sets). Patient samples were clustered using ConsensusClusterPlus analysis based on the expression levels of 12 genes involved in arachidonic acid metabolism that were significantly associated with HCC prognosis. Differentially expressed genes (DEGs) within different clusters were distinguished and compared using WebGestaltR. Immunohistochemistry (IHC) analysis was performed using a human HCC tissue microarray (TMA). Tumor immune microenvironment assessment was performed using ESTIMATE, ssGSEA, and TIDE. RESULTS: Samples of patients with HCC were classified into three clusters, with significant differences in OS. Cluster 2 showed the best prognosis, whereas cluster 1 presented the worst. The three clusters showed significant differences in immune infiltration. We then performed Cox and LASSO regression analyses, which revealed CYP2C9, G6PD, CDC20, SPP1, PON1, TRNP1, and ADH4 as prognosis-related hub genes, making it a simplified prognostic model. TMA analysis for the seven target genes showed similar results of regression analyses. The high-risk group showed a significantly worse prognosis and reduced immunotherapy efficacy. Our model showed stable prognostic predictive efficacy. CONCLUSIONS: This seven-gene-based model showed stable outcomes in predicting HCC prognosis as well as responses to immunotherapy.
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We then performed Cox and LASSO regression analyses, which revealed CYP2C9, G6PD, CDC20, SPP1, PON1, TRNP1, and ADH4 as prognosis‐related hub genes, making it a simplified prognostic model.
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We then performed Cox and LASSO regression analyses, which revealed CYP2C9, G6PD, CDC20, SPP1, PON1, TRNP1, and ADH4 as prognosis‐related hub genes, making it a simplified prognostic model.
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All data generated or analyzed during this study are included in this published article [and its supplementary information files].
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sections[31] "Data Availability Statement" paragraph 2
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All data generated or analyzed during this study are included in this published article [and its supplementary information files].
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This seven‐gene–based model showed stable outcomes in predicting HCC prognosis as well as responses to immunotherapy.
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This seven‐gene–based model showed stable outcomes in predicting HCC prognosis as well as responses to immunotherapy.
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This seven‐gene–based model showed stable outcomes in predicting HCC prognosis as well as responses to immunotherapy.
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GSM363371
[425]
GSM363372
[426]
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[427]
GSM363374
[428]
GSM363375
[429]
GSM363376
[430]
GSM363378
[431]
GSM363380
[432]
GSM363381
[433]
GSM363382
[434]
GSM363384
[435]
GSM363386
[436]
GSM363388
[437]
GSM363391
[438]
GSM363393
[439]
GSM363397
[440]
GSM363400
[441]
GSM363402
[442]
GSM363404
[443]
GSM363407
[444]
GSM363417
[445]
GSM363420
[446]
GSM363421
[447]
GSM363422
[448]
GSM363423
[449]
GSM363424
[450]
GSM363425
[451]
GSM363426
[452]
GSM363427
[453]
GSM363428
[454]
GSM363429
[455]
GSM363430
[456]
GSM363431
[457]
GSM363432
[458]
GSM363433
[459]
GSM363434
[460]
GSM363435
[461]
GSM363436
[462]
GSM363437
[463]
GSM363438
[464]
GSM363439
[465]
GSM363440
[466]
GSM363441
[467]
GSM363442
[468]
GSM363443
[469]
GSM363444
[470]
GSM363445
[471]
GSM363446
[472]
GSM363447
[473]
GSM363448
[474]
GSM363449
[475]
GSM363450
[476]
GSM363451
[477]
GSM712532
[478]
GSM712533
[479]
GSM712534
[480]
GSM712535
[481]
GSM712536
[482]
GSM712537
[483]
GSM712538
[484]
GSM712539
[485]
GSM712540
[486]
GSM712541
[487]
GSM712542
sample_count
488
group_sizes
null
group_sizes_basis
null
platform
3921;571
taxon
Homo sapiens
title
Gene expression data of human hepatocellular carcinoma (HCC)
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[3] object · 15 fields
id
data:geo:GSE76427
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=GSE76427
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE76427
version
null
note
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
access_statement_kind
data_availability_statement
sample_accessions array · 167 items
[0]
GSM2011285
[1]
GSM2011286
[2]
GSM2011287
[3]
GSM2011288
[4]
GSM2011289
[5]
GSM2011290
[6]
GSM2011291
[7]
GSM2011292
[8]
GSM2011293
[9]
GSM2011294
[10]
GSM2011295
[11]
GSM2011296
[12]
GSM2011297
[13]
GSM2011298
[14]
GSM2011299
[15]
GSM2011300
[16]
GSM2011301
[17]
GSM2011302
[18]
GSM2011303
[19]
GSM2011304
[20]
GSM2011305
[21]
GSM2011306
[22]
GSM2011307
[23]
GSM2011308
[24]
GSM2011309
[25]
GSM2011310
[26]
GSM2011311
[27]
GSM2011312
[28]
GSM2011313
[29]
GSM2011314
[30]
GSM2011315
[31]
GSM2011316
[32]
GSM2011317
[33]
GSM2011318
[34]
GSM2011319
[35]
GSM2011320
[36]
GSM2011321
[37]
GSM2011322
[38]
GSM2011323
[39]
GSM2011324
[40]
GSM2011325
[41]
GSM2011326
[42]
GSM2011327
[43]
GSM2011328
[44]
GSM2011329
[45]
GSM2011330
[46]
GSM2011331
[47]
GSM2011332
[48]
GSM2011333
[49]
GSM2011334
[50]
GSM2011335
[51]
GSM2011336
[52]
GSM2011337
[53]
GSM2011338
[54]
GSM2011339
[55]
GSM2011340
[56]
GSM2011341
[57]
GSM2011342
[58]
GSM2011343
[59]
GSM2011344
[60]
GSM2011345
[61]
GSM2011346
[62]
GSM2011347
[63]
GSM2011348
[64]
GSM2011349
[65]
GSM2011350
[66]
GSM2011351
[67]
GSM2011352
[68]
GSM2011353
[69]
GSM2011354
[70]
GSM2011355
[71]
GSM2011356
[72]
GSM2011357
[73]
GSM2011358
[74]
GSM2011359
[75]
GSM2011360
[76]
GSM2011361
[77]
GSM2011362
[78]
GSM2011363
[79]
GSM2011364
[80]
GSM2011365
[81]
GSM2011366
[82]
GSM2011367
[83]
GSM2011368
[84]
GSM2011369
[85]
GSM2011370
[86]
GSM2011371
[87]
GSM2011372
[88]
GSM2011373
[89]
GSM2011374
[90]
GSM2011375
[91]
GSM2011376
[92]
GSM2011377
[93]
GSM2011378
[94]
GSM2011379
[95]
GSM2011380
[96]
GSM2011381
[97]
GSM2011382
[98]
GSM2011383
[99]
GSM2011384
[100]
GSM2011385
[101]
GSM2011386
[102]
GSM2011387
[103]
GSM2011388
[104]
GSM2011389
[105]
GSM2011390
[106]
GSM2011391
[107]
GSM2011392
[108]
GSM2011393
[109]
GSM2011394
[110]
GSM2011395
[111]
GSM2011396
[112]
GSM2011397
[113]
GSM2011398
[114]
GSM2011399
[115]
GSM2011400
[116]
GSM2011401
[117]
GSM2011402
[118]
GSM2011403
[119]
GSM2011404
[120]
GSM2011405
[121]
GSM2011406
[122]
GSM2011407
[123]
GSM2011408
[124]
GSM2011409
[125]
GSM2011410
[126]
GSM2011411
[127]
GSM2011412
[128]
GSM2011413
[129]
GSM2011414
[130]
GSM2011415
[131]
GSM2011416
[132]
GSM2011417
[133]
GSM2011418
[134]
GSM2011419
[135]
GSM2011420
[136]
GSM2011421
[137]
GSM2011422
[138]
GSM2011423
[139]
GSM2011424
[140]
GSM2011425
[141]
GSM2011426
[142]
GSM2011427
[143]
GSM2011428
[144]
GSM2011429
[145]
GSM2011430
[146]
GSM2011431
[147]
GSM2011432
[148]
GSM2011433
[149]
GSM2011434
[150]
GSM2011435
[151]
GSM2011436
[152]
GSM2011437
[153]
GSM2011438
[154]
GSM2011439
[155]
GSM2011440
[156]
GSM2011441
[157]
GSM2011442
[158]
GSM2011443
[159]
GSM2011444
[160]
GSM2011445
[161]
GSM2011446
[162]
GSM2011447
[163]
GSM2011448
[164]
GSM2011449
[165]
GSM2011450
[166]
GSM2011451
sample_count
167
group_sizes
null
group_sizes_basis
null
platform
10558
taxon
Homo sapiens
title
Microarray expression data for tumor and adjacent non-tumor tissues from hepatocellular carcinoma patients
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[4] object · 15 fields
id
data:geo:GSE78220
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=GSE78220
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE78220
version
null
note
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
access_statement_kind
data_availability_statement
sample_accessions array · 28 items
[0]
GSM2069823
[1]
GSM2069824
[2]
GSM2069825
[3]
GSM2069826
[4]
GSM2069827
[5]
GSM2069828
[6]
GSM2069829
[7]
GSM2069830
[8]
GSM2069831
[9]
GSM2069832
[10]
GSM2069833
[11]
GSM2069834
[12]
GSM2069835
[13]
GSM2069836
[14]
GSM2069837
[15]
GSM2069838
[16]
GSM2069839
[17]
GSM2069840
[18]
GSM2069841
[19]
GSM2069842
[20]
GSM2069843
[21]
GSM2069844
[22]
GSM2069845
[23]
GSM2069846
[24]
GSM2069847
[25]
GSM2069848
[26]
GSM2069849
[27]
GSM2069850
sample_count
28
group_sizes
null
group_sizes_basis
null
platform
11154
taxon
Homo sapiens
title
mRNA expressions in pre-treatment melanomas undergoing anti-PD-1 checkpoint inhibition therapy
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[5] object · 15 fields
id
data:geo:GSE91061
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=GSE91061
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE91061
version
null
note
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
access_statement_kind
data_availability_statement
sample_accessions array · 109 items
[0]
GSM2420259
[1]
GSM2420260
[2]
GSM2420261
[3]
GSM2420262
[4]
GSM2420263
[5]
GSM2420264
[6]
GSM2420265
[7]
GSM2420266
[8]
GSM2420267
[9]
GSM2420268
[10]
GSM2420269
[11]
GSM2420270
[12]
GSM2420271
[13]
GSM2420272
[14]
GSM2420273
[15]
GSM2420274
[16]
GSM2420275
[17]
GSM2420276
[18]
GSM2420277
[19]
GSM2420278
[20]
GSM2420279
[21]
GSM2420280
[22]
GSM2420281
[23]
GSM2420282
[24]
GSM2420283
[25]
GSM2420284
[26]
GSM2420285
[27]
GSM2420286
[28]
GSM2420287
[29]
GSM2420288
[30]
GSM2420289
[31]
GSM2420290
[32]
GSM2420291
[33]
GSM2420292
[34]
GSM2420293
[35]
GSM2420294
[36]
GSM2420295
[37]
GSM2420296
[38]
GSM2420297
[39]
GSM2420298
[40]
GSM2420299
[41]
GSM2420300
[42]
GSM2420301
[43]
GSM2420302
[44]
GSM2420303
[45]
GSM2420304
[46]
GSM2420305
[47]
GSM2420306
[48]
GSM2420307
[49]
GSM2420308
[50]
GSM2420310
[51]
GSM2420311
[52]
GSM2420312
[53]
GSM2420313
[54]
GSM2420316
[55]
GSM2420317
[56]
GSM2420318
[57]
GSM2420319
[58]
GSM2420320
[59]
GSM2420323
[60]
GSM2420324
[61]
GSM2420325
[62]
GSM2420326
[63]
GSM2420328
[64]
GSM2420329
[65]
GSM2420331
[66]
GSM2420332
[67]
GSM2420333
[68]
GSM2420334
[69]
GSM2420335
[70]
GSM2420336
[71]
GSM2420337
[72]
GSM2420338
[73]
GSM2420339
[74]
GSM2420340
[75]
GSM2420341
[76]
GSM2420342
[77]
GSM2420343
[78]
GSM2420344
[79]
GSM2420345
[80]
GSM2420346
[81]
GSM2420349
[82]
GSM2420350
[83]
GSM2420351
[84]
GSM2420352
[85]
GSM2420353
[86]
GSM2420354
[87]
GSM2420355
[88]
GSM2420356
[89]
GSM2420357
[90]
GSM2420358
[91]
GSM2420359
[92]
GSM2420360
[93]
GSM2420361
[94]
GSM2420362
[95]
GSM2420363
[96]
GSM2420364
[97]
GSM2420365
[98]
GSM2420366
[99]
GSM2420367
[100]
GSM2420368
[101]
GSM2420369
[102]
GSM2420370
[103]
GSM2420371
[104]
GSM2420372
[105]
GSM2420373
[106]
GSM2420374
[107]
GSM2420375
[108]
GSM2420376
sample_count
109
group_sizes
null
group_sizes_basis
null
platform
9052
taxon
Homo sapiens
title
Molecular portraits of tumor mutational and micro-environmental sculpting by immune checkpoint blockade therapy
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 10 items
[0]
asset:data:geo:GSE135222 not downloaded
[1]
asset:data:geo:GSE135222 licence not read
[2]
asset:data:geo:GSE14520 not downloaded
[3]
asset:data:geo:GSE14520 licence not read
[4]
asset:data:geo:GSE76427 not downloaded
[5]
asset:data:geo:GSE76427 licence not read
[6]
asset:data:geo:GSE78220 not downloaded
[7]
asset:data:geo:GSE78220 licence not read
[8]
asset:data:geo:GSE91061 not downloaded
[9]
asset:data:geo:GSE91061 licence not read
analysis object · 4 fields
state
complete
methods array · 1 item
[0] object · 10 fields
id
method-1
family
survival_analysis
specific
cox_proportional_hazards
label
Survival analysis
dsl_operations array · 1 item
[0]
cox_ph
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
1
band
verbatim
quote
We then performed Cox and LASSO regression analyses, which revealed CYP2C9, G6PD, CDC20, SPP1, PON1, TRNP1, and ADH4 as prognosis‐related hub genes, making it a simplified prognostic model.
targets array · 0 items
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 1 item
[0]
cox_ph
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 5 items
[0]
GSE14520
[1]
GSE76427
[2]
GSE91061
[3]
GSE78220
[4]
GSE135222
resolved_accessions array · 5 items
[0]
GSE14520
[1]
GSE76427
[2]
GSE91061
[3]
GSE78220
[4]
GSE135222
statements array · 1 item
[0]
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
basis
The paper names GSE14520, GSE76427, GSE91061, GSE78220, GSE135222 in NCBI 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:39540710
[1]
data:geo:GSE135222
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:GSE135222
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
2026-11-01T19:38:39Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
13653
completion_tokens
3260
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:39540710
type
paper
label
pmid:39540710
[1] object · 3 fields
id
source:pmid:39540710
type
manuscript
label
PMID 39540710 full text
[2] object · 3 fields
id
data:geo:GSE135222
type
dataset
label
GEO GSE135222
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:39540710
type
paper
label
pmid:39540710
[1] object · 3 fields
id
source:pmid:39540710
type
manuscript
label
PMID 39540710 full text
[2] object · 3 fields
id
data:geo:GSE135222
type
dataset
label
GEO GSE135222
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-39540710
type
extraction
used array · 1 item
[0]
source:pmid:39540710
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE135222
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE135222
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:39540710
parent_hash
sha256:cc907c943e54a9a89bf306ab41cf5d5e8d6419118861c30e74732a104cd3bfc2
fork_of
null
gaps array · 14 items
[0]
asset:data:geo:GSE135222 licence not read
[1]
asset:data:geo:GSE135222 not downloaded
[2]
asset:data:geo:GSE14520 licence not read
[3]
asset:data:geo:GSE14520 not downloaded
[4]
asset:data:geo:GSE76427 licence not read
[5]
asset:data:geo:GSE76427 not downloaded
[6]
asset:data:geo:GSE78220 licence not read
[7]
asset:data:geo:GSE78220 not downloaded
[8]
asset:data:geo:GSE91061 licence not read
[9]
asset:data:geo:GSE91061 not downloaded
[10]
execution.not_run
[11]
review.human_critique
[12]
review.independent_reader
[13]
review.machine_critique
assays array · 3 items
[0] object · 11 fields
role
data_generation
definition_version
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istinguished and compared using WebGestaltR. Immunohistochemistry (IHC) analysis was performed using a human H
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lysis was performed using a human HCC tissue microarray (TMA). Tumor immune microenvironment assessm
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We then performed Cox and LASSO regression analyses, which revealed CYP2C9, G6PD, CDC20, SPP1, PON1, TRNP1, and ADH4 as prognosis‐related hub genes, making it a simplified prognostic model.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39540710", "kind": "science-record", "revision": 3, "content_hash": "sha256:9ebf42976d11f51ce6d39ad734d9aa612d67ea15896361ed652913ae9109f53e", "created_at": "2026-11-01T20:29:48Z", "updated_at": "2026-11-01T22:55:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Predictive Prognostic Model for Hepatocellular Carcinoma Based on Seven Genes Participating in Arachidonic Acid Metabolism.", "doi": "10.1002/cam4.70284", "pmid": "39540710", "authors": ["Xinyu Gu", "Jing Wang", "Jun Guan", "Guojun Li", "Xiao Ma", "Yanli Ren", "Shanshan Wu", "Chao Chen", "Haihong Zhu"], "journal": "Cancer medicine", "year": 2024, "abstract": "BACKGROUND: The occult onset and rapid progression of hepatocellular carcinoma (HCC) lead to an unsatisfactory overall survival (OS) rate. Established prognostic predictive models based on tumor-node-metastasis staging and predictive factors do not report satisfactory predictive efficacy. Arachidonic acid plays pivotal roles in biological processes including inflammation, regeneration, immune modulation, and tumorigenesis. We, therefore, constructed a prognostic predictive model based on seven genes linked to arachidonic acid metabolism, using samples of HCC patients from databases to analyze the genomic profiles. We also assessed the predictive stability of the constructed model.\nMETHODS: Sample data of 365 patients diagnosed with HCC were extracted from The Cancer Genome Atlas (TCGA, training set) and HCCDB18, GSE14520, and GSE76427 databases (validation sets). Patient samples were clustered using ConsensusClusterPlus analysis based on the expression levels of 12 genes involved in arachidonic acid metabolism that were significantly associated with HCC prognosis. Differentially expressed genes (DEGs) within different clusters were distinguished and compared using WebGestaltR. Immunohistochemistry (IHC) analysis was performed using a human HCC tissue microarray (TMA). Tumor immune microenvironment assessment was performed using ESTIMATE, ssGSEA, and TIDE.\nRESULTS: Samples of patients with HCC were classified into three clusters, with significant differences in OS. Cluster 2 showed the best prognosis, whereas cluster 1 presented the worst. The three clusters showed significant differences in immune infiltration. We then performed Cox and LASSO regression analyses, which revealed CYP2C9, G6PD, CDC20, SPP1, PON1, TRNP1, and ADH4 as prognosis-related hub genes, making it a simplified prognostic model. TMA analysis for the seven target genes showed similar results of regression analyses. The high-risk group showed a significantly worse prognosis and reduced immunotherapy efficacy. Our model showed stable prognostic predictive efficacy.\nCONCLUSIONS: This seven-gene-based model showed stable outcomes in predicting HCC prognosis as well as responses to immunotherapy.", "claims": [{"id": "claim-method", "statement": "We then performed Cox and LASSO regression analyses, which revealed CYP2C9, G6PD, CDC20, SPP1, PON1, TRNP1, and ADH4 as prognosis‐related hub genes, making it a simplified prognostic model.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39540710", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We then performed Cox and LASSO regression analyses, which revealed CYP2C9, G6PD, CDC20, SPP1, PON1, TRNP1, and ADH4 as prognosis‐related hub genes, making it a simplified prognostic model."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analyzed during this study are included in this published article [and its supplementary information files].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39540710", "locator": "sections[31] \"Data Availability Statement\" paragraph 2", "quote": "All data generated or analyzed during this study are included in this published article [and its supplementary information files]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "This seven‐gene–based model showed stable outcomes in predicting HCC prognosis as well as responses to immunotherapy.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39540710", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "This seven‐gene–based model showed stable outcomes in predicting HCC prognosis as well as responses to immunotherapy."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "This seven‐gene–based model showed stable outcomes in predicting HCC prognosis as well as responses to immunotherapy.", "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:39540710"], "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:GSE135222"], "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:GSE135222"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39540710", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1002/cam4.70284", "sha256": 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