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pmid:34466015

Predictive Models for HCC Prognosis, Recurrence Risk, and Immune Infiltration Based on Two Exosomal Genes: MYL6B and THOC2.

Jinyu Zhu · Bufu Tang · Yang Gao · Suqin Xu · Jianfei Tu · Yajie Wang · Weibin Yang · Shiji Fang · Qiaoyou Weng · Zhongwei Zhao · Min Xu · Yang Yang · Minjiang Chen · Chenying Lu · Jiansong Ji

Journal of inflammation research · 2021 doi:10.2147/JIR.S315957

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title
Predictive Models for HCC Prognosis, Recurrence Risk, and Immune Infiltration Based on Two Exosomal Genes: MYL6B and THOC2.
doi
10.2147/JIR.S315957
pmid
34466015
authors array · 15 items
[0]
Jinyu Zhu
[1]
Bufu Tang
[2]
Yang Gao
[3]
Suqin Xu
[4]
Jianfei Tu
[5]
Yajie Wang
[6]
Weibin Yang
[7]
Shiji Fang
[8]
Qiaoyou Weng
[9]
Zhongwei Zhao
[10]
Min Xu
[11]
Yang Yang
[12]
Minjiang Chen
[13]
Chenying Lu
[14]
Jiansong Ji
journal
Journal of inflammation research
year
2021
abstract
INTRODUCTION: Hepatocellular carcinoma (HCC) is a heterogeneous molecular disease with complex molecular pathogenesis that influences the efficacy of therapies. Exosomes play a crucial role in tumorigenesis and poor disease outcomes in HCC. OBJECTIVE: The aim of this study was to identify the optimal gene set derived from exosomes in HCC with substantial predictive value to construct models for determining prognosis, recurrence risk and diagnosis and to identify candidates suitable for immunotherapy and chemotherapy, thereby providing new ideas for the individualized treatment of patients and for improving prognosis. METHODS: Weighted correlation network analysis (WGCNA) and univariate and multivariate Cox PH regression analyses were applied to identify exosome-related signatures in the TCGA and exoRbase databases associated with clinical relevance, immunogenic features and tumor progression in HCC. Cell experiments were performed to further confirm the oncogenic effect of MYL6B and THOC2. RESULTS: The models for prognosis and recurrence risk prediction were built based on two exosomal genes (MYL6B and THOC2) and were confirmed to be independent predictive factors with superior predictive performance. Patients with high prognostic risk had poorer prognosis than patients with low prognostic risk in all HCC datasets, namely, the TCGA cohort (HR=2.5, P<0.001), the ICGC cohort (HR=3.15, P<0.001) and the GSE14520 cohort (HR=1.85, P=0.004). A higher recurrence probability was found in HCC patients with high recurrence risk than in HCC patients with low recurrence risk in the TCGA cohort (HR=2.44, P<0.001) and the GSE14520 cohort (HR=1.54, P=0.025). High prognostic risk patients had higher expression of immune checkpoint genes, such as PD1, B7H3, B7H5, CTLA4 and TIM3 (P<0.05). Diagnostic models based on the same two genes were able to accurately distinguish HCC patients from normal individuals and HCC from dysplastic nodules. CONCLUSION: Our findings lay the foundation for identifying molecular markers to increase the early detection rate of HCC, improve disease outcomes, and determine more effective individualized treatment options for patients.
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The comparison of the mean of two independent samples was performed by Student’s t-test or Wilcoxon test.
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The data and materials used to support the findings of this study are available from the corresponding author upon request.
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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
[2] object · 15 fields
id
data:geo:GSE6764
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=GSE6764
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE6764
version
null
note
The data and materials used to support the findings of this study are available from the corresponding author upon request.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The data and materials used to support the findings of this study are available from the corresponding author upon request.
access_statement_kind
data_availability_statement
sample_accessions array · 75 items
[0]
GSM155919
[1]
GSM155920
[2]
GSM155921
[3]
GSM155922
[4]
GSM155923
[5]
GSM155924
[6]
GSM155925
[7]
GSM155926
[8]
GSM155927
[9]
GSM155928
[10]
GSM155929
[11]
GSM155930
[12]
GSM155931
[13]
GSM155932
[14]
GSM155933
[15]
GSM155934
[16]
GSM155935
[17]
GSM155936
[18]
GSM155937
[19]
GSM155938
[20]
GSM155939
[21]
GSM155940
[22]
GSM155941
[23]
GSM155942
[24]
GSM155943
[25]
GSM155944
[26]
GSM155945
[27]
GSM155946
[28]
GSM155947
[29]
GSM155948
[30]
GSM155949
[31]
GSM155950
[32]
GSM155951
[33]
GSM155952
[34]
GSM155953
[35]
GSM155954
[36]
GSM155955
[37]
GSM155956
[38]
GSM155957
[39]
GSM155958
[40]
GSM155959
[41]
GSM155960
[42]
GSM155961
[43]
GSM155962
[44]
GSM155963
[45]
GSM155964
[46]
GSM155965
[47]
GSM155966
[48]
GSM155967
[49]
GSM155968
[50]
GSM155969
[51]
GSM155970
[52]
GSM155971
[53]
GSM155972
[54]
GSM155973
[55]
GSM155974
[56]
GSM155975
[57]
GSM155976
[58]
GSM155977
[59]
GSM155978
[60]
GSM155979
[61]
GSM155980
[62]
GSM155981
[63]
GSM155982
[64]
GSM155983
[65]
GSM155984
[66]
GSM155985
[67]
GSM155986
[68]
GSM155987
[69]
GSM155988
[70]
GSM155989
[71]
GSM155990
[72]
GSM155991
[73]
GSM155992
[74]
GSM155993
sample_count
75
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[3] object · 15 fields
id
data:geo:GSE89377
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=GSE89377
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE89377
version
null
note
The data and materials used to support the findings of this study are available from the corresponding author upon request.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The data and materials used to support the findings of this study are available from the corresponding author upon request.
access_statement_kind
data_availability_statement
sample_accessions array · 107 items
[0]
GSM2367554
[1]
GSM2367555
[2]
GSM2367556
[3]
GSM2367557
[4]
GSM2367558
[5]
GSM2367559
[6]
GSM2367560
[7]
GSM2367561
[8]
GSM2367562
[9]
GSM2367563
[10]
GSM2367564
[11]
GSM2367565
[12]
GSM2367566
[13]
GSM2367567
[14]
GSM2367568
[15]
GSM2367569
[16]
GSM2367570
[17]
GSM2367571
[18]
GSM2367572
[19]
GSM2367573
[20]
GSM2367574
[21]
GSM2367575
[22]
GSM2367576
[23]
GSM2367577
[24]
GSM2367578
[25]
GSM2367579
[26]
GSM2367580
[27]
GSM2367581
[28]
GSM2367582
[29]
GSM2367583
[30]
GSM2367584
[31]
GSM2367585
[32]
GSM2367586
[33]
GSM2367587
[34]
GSM2367588
[35]
GSM2367589
[36]
GSM2367590
[37]
GSM2367591
[38]
GSM2367592
[39]
GSM2367593
[40]
GSM2367594
[41]
GSM2367595
[42]
GSM2367596
[43]
GSM2367597
[44]
GSM2367598
[45]
GSM2367599
[46]
GSM2367600
[47]
GSM2367601
[48]
GSM2367602
[49]
GSM2367603
[50]
GSM2367604
[51]
GSM2367605
[52]
GSM2367606
[53]
GSM2367607
[54]
GSM2367608
[55]
GSM2367609
[56]
GSM2367610
[57]
GSM2367611
[58]
GSM2367612
[59]
GSM2367613
[60]
GSM2367614
[61]
GSM2367615
[62]
GSM2367616
[63]
GSM2367617
[64]
GSM2367618
[65]
GSM2367619
[66]
GSM2367620
[67]
GSM2367621
[68]
GSM2367622
[69]
GSM2367623
[70]
GSM2367624
[71]
GSM2367625
[72]
GSM2367626
[73]
GSM2367627
[74]
GSM2367628
[75]
GSM2367629
[76]
GSM2367630
[77]
GSM2367631
[78]
GSM2367632
[79]
GSM2367633
[80]
GSM2367634
[81]
GSM2367635
[82]
GSM2367636
[83]
GSM2367637
[84]
GSM2367638
[85]
GSM2367639
[86]
GSM2367640
[87]
GSM2367641
[88]
GSM2367642
[89]
GSM2367643
[90]
GSM2367644
[91]
GSM2367645
[92]
GSM2367646
[93]
GSM2367647
[94]
GSM2367648
[95]
GSM2367649
[96]
GSM2367650
[97]
GSM2367651
[98]
GSM2367652
[99]
GSM2367653
[100]
GSM2367654
[101]
GSM2367655
[102]
GSM2367656
[103]
GSM2367657
[104]
GSM2367658
[105]
GSM2367659
[106]
GSM2367660
sample_count
107
group_sizes
null
group_sizes_basis
null
platform
6947
taxon
Homo sapiens
title
Identifying novel drivers of human hepatocellular carcinoma and revealing clinical relevance as early diagnostic and prognostic biomarker
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 · 6 items
[0]
asset:data:geo:GSE14520 not downloaded
[1]
asset:data:geo:GSE14520 licence not read
[2]
asset:data:geo:GSE6764 not downloaded
[3]
asset:data:geo:GSE6764 licence not read
[4]
asset:data:geo:GSE89377 not downloaded
[5]
asset:data:geo:GSE89377 licence not read
analysis object · 4 fields
state
partial
methods array · 3 items
[0] object · 10 fields
id
method-1
family
group_comparison
specific
wilcoxon
label
Group comparison
dsl_operations array · 0 items
missing_operations array · 1 item
[0]
group_comparison_wilcoxon
expressible
false
parameters object · 0 fields
data_shapes array · 1 item
[0]
two_or_more_groups_continuous
evidence object · 3 fields
score
1
band
verbatim
quote
The comparison of the mean of two independent samples was performed by Student’s t-test or Wilcoxon test.
[1] object · 10 fields
id
method-2
family
survival_analysis
specific
kaplan_meier
label
Survival analysis
dsl_operations array · 1 item
[0]
survival_km
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
Kaplan-Meier
[2] object · 10 fields
id
method-3
family
diagnostic_evaluation
specific
roc
label
Diagnostic test evaluation
dsl_operations array · 6 items
[0]
confusion_counts
[1]
roc_curve
[2]
sensitivity_specificity
[3]
solve_confusion_matrix
[4]
classification_metrics
[5]
published_precision_envelope
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
reference_standard_and_test
evidence object · 3 fields
score
0.8
band
high
quote
ROC curve
targets array · 0 items
gaps array · 1 item
[0]
method.group_comparison_wilcoxon
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
false
required_operations array · 0 items
missing_operations array · 1 item
[0]
group_comparison_wilcoxon
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 3 items
[0]
GSE14520
[1]
GSE6764
[2]
GSE89377
resolved_accessions array · 3 items
[0]
GSE14520
[1]
GSE6764
[2]
GSE89377
statements array · 1 item
[0]
The data and materials used to support the findings of this study are available from the corresponding author upon request.
basis
The paper names GSE14520, GSE6764, GSE89377 in 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 · 0 items
assets array · 2 items
[0]
source:pmid:34466015
[1]
data:geo:GSE14520
steps array · 0 items
must_build object · 5 fields
dsl_operations array · 1 item
[0] object · 3 fields
operation
group_comparison_wilcoxon
priority
null
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE14520
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
2026-10-31T18:34:18Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
46333
completion_tokens
2793
cached_tokens
15624
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:34466015
type
paper
label
pmid:34466015
[1] object · 3 fields
id
source:pmid:34466015
type
manuscript
label
PMID 34466015 full text
[2] object · 3 fields
id
data:geo:GSE14520
type
dataset
label
GEO GSE14520
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:34466015
type
paper
label
pmid:34466015
[1] object · 3 fields
id
source:pmid:34466015
type
manuscript
label
PMID 34466015 full text
[2] object · 3 fields
id
data:geo:GSE14520
type
dataset
label
GEO GSE14520
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-34466015
type
extraction
used array · 1 item
[0]
source:pmid:34466015
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE14520
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE14520
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:34466015
parent_hash
sha256:248aef84608dc09e91e3e3dfc98071e7b84eaea8c2811cce472318578fa5e076
fork_of
null
gaps array · 12 items
[0]
asset:data:geo:GSE14520 licence not read
[1]
asset:data:geo:GSE14520 not downloaded
[2]
asset:data:geo:GSE6764 licence not read
[3]
asset:data:geo:GSE6764 not downloaded
[4]
asset:data:geo:GSE89377 licence not read
[5]
asset:data:geo:GSE89377 not downloaded
[6]
execution.not_run
[7]
method.group_comparison_wilcoxon
[8]
review.human_critique
[9]
review.independent_reader
[10]
review.machine_critique
[11]
step:run_analysis blocked on method:group_comparison_wilcoxon
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 · 4 items
[0]
Materials and Methods Cell Culture and Transfection SK-HEP1 and HCCLM3 cell lines were purchased
[1]
% CO2 and 95% relative humidity at 37°C. The transfection process is briefly described as follows: MYL
[2]
n, California, USA) was used to achieve cell transfection with these siRNAs. SK-HEP1 and HCCLM3 cell l
[3]
upplemented with serum. The sequences of the knockdown and control siRNAs are listed in the support
order_basis
paper_text_order:2302
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 · 3 items
[0]
n (ATCC) (Manassas, VA, USA). The cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM) su
[1]
pended in DMEM supplemented with 10% FBS and cultured in a 6-well plate at a density of approximately
[2]
mixture was removed and the cells were then cultured in medium supplemented with serum. The sequence
order_basis
paper_text_order:2439
id
assay:2
[2] object · 11 fields
role
analysis
definition_id
group_comparison
definition_version
f2132e96ae6c7a4e
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
The comparison of the mean of two independent samples was performed by Student’s t-test or Wilcoxon test.
order_basis
consumes_earlier_output
id
assay:3
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34466015", "kind": "science-record", "revision": 7, "content_hash": "sha256:98260565d4fc5e7ac7a6dac5a5879c0dbe2e85f8f6d11c92bb5e7adcb282cfb4", "created_at": "2026-11-01T15:41:50Z", "updated_at": "2026-11-01T22:04:37Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Predictive Models for HCC Prognosis, Recurrence Risk, and Immune Infiltration Based on Two Exosomal Genes: MYL6B and THOC2.", "doi": "10.2147/JIR.S315957", "pmid": "34466015", "authors": ["Jinyu Zhu", "Bufu Tang", "Yang Gao", "Suqin Xu", "Jianfei Tu", "Yajie Wang", "Weibin Yang", "Shiji Fang", "Qiaoyou Weng", "Zhongwei Zhao", "Min Xu", "Yang Yang", "Minjiang Chen", "Chenying Lu", "Jiansong Ji"], "journal": "Journal of inflammation research", "year": 2021, "abstract": "INTRODUCTION: Hepatocellular carcinoma (HCC) is a heterogeneous molecular disease with complex molecular pathogenesis that influences the efficacy of therapies. Exosomes play a crucial role in tumorigenesis and poor disease outcomes in HCC.\nOBJECTIVE: The aim of this study was to identify the optimal gene set derived from exosomes in HCC with substantial predictive value to construct models for determining prognosis, recurrence risk and diagnosis and to identify candidates suitable for immunotherapy and chemotherapy, thereby providing new ideas for the individualized treatment of patients and for improving prognosis.\nMETHODS: Weighted correlation network analysis (WGCNA) and univariate and multivariate Cox PH regression analyses were applied to identify exosome-related signatures in the TCGA and exoRbase databases associated with clinical relevance, immunogenic features and tumor progression in HCC. Cell experiments were performed to further confirm the oncogenic effect of MYL6B and THOC2.\nRESULTS: The models for prognosis and recurrence risk prediction were built based on two exosomal genes (MYL6B and THOC2) and were confirmed to be independent predictive factors with superior predictive performance. Patients with high prognostic risk had poorer prognosis than patients with low prognostic risk in all HCC datasets, namely, the TCGA cohort (HR=2.5, P<0.001), the ICGC cohort (HR=3.15, P<0.001) and the GSE14520 cohort (HR=1.85, P=0.004). A higher recurrence probability was found in HCC patients with high recurrence risk than in HCC patients with low recurrence risk in the TCGA cohort (HR=2.44, P<0.001) and the GSE14520 cohort (HR=1.54, P=0.025). High prognostic risk patients had higher expression of immune checkpoint genes, such as PD1, B7H3, B7H5, CTLA4 and TIM3 (P<0.05). 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The transfection process is briefly described as follows: MYL", "n, California, USA) was used to achieve cell transfection with these siRNAs. SK-HEP1 and HCCLM3 cell l", "upplemented with serum. The sequences of the knockdown and control siRNAs are listed in the support"], "order_basis": "paper_text_order:2302", "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": ["n (ATCC) (Manassas, VA, USA). The cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM) su", "pended in DMEM supplemented with 10% FBS and cultured in a 6-well plate at a density of approximately", "mixture was removed and the cells were then cultured in medium supplemented with serum. 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