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pmid:30538557

Large-scale analysis reveals a novel risk score to predict overall survival in hepatocellular carcinoma.

Yujia Zheng · Yulin Liu · Songfeng Zhao · Zhetian Zheng · Chunyi Shen · Li An · Yongliang Yuan

Cancer management and research · 2018 doi:10.2147/CMAR.S181396

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Experiment

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Data

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pmid:30538557
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title
Large-scale analysis reveals a novel risk score to predict overall survival in hepatocellular carcinoma.
doi
10.2147/CMAR.S181396
pmid
30538557
authors array · 7 items
[0]
Yujia Zheng
[1]
Yulin Liu
[2]
Songfeng Zhao
[3]
Zhetian Zheng
[4]
Chunyi Shen
[5]
Li An
[6]
Yongliang Yuan
journal
Cancer management and research
year
2018
abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality and an increasing incidence worldwide; however, there are very few effective diagnostic approaches and prognostic biomarkers. MATERIALS AND METHODS: One hundred forty-nine pairs of HCC samples from Gene Expression Omnibus (GEO) were obtained to screen differentially expressed genes (DEGs) between HCC and normal samples. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene ontology enrichment analyses, and protein-protein interaction network were used. Cox proportional hazards regression analysis was used to identify significant prognostic DEGs, with which a gene expression signature prognostic prediction model was identified in The Cancer Genome Atlas (TCGA) project discovery cohort. The robustness of this panel was assessed in the GSE14520 cohort. We verified details of the gene expression level of the key molecules through TCGA, GEO, and qPCR and used immunohistochemistry for substantiation in HCC tissues. The methylation states of these genes were also explored. RESULTS: Ninety-eight genes, consisting of 13 upregulated and 85 downregulated genes, were screened out in three datasets. KEGG and Gene ontology analysis for the DEGs revealed important biological features of each subtype. Protein-protein interaction network analysis was constructed, consisting of 64 nodes and 115 edges. A subset of four genes (SPINK1, TXNRD1, LCAT, and PZP) that formed a prognostic gene expression signature was established from TCGA and validated in GSE14520. Next, the expression details of the four genes were validated with TCGA, GEO, and clinical samples. The expression panels of the four genes were closely related to methylation states. CONCLUSION: This study identified a novel four-gene signature biomarker for predicting the prognosis of HCC. The biomarkers may also reveal molecular mechanisms underlying development of the disease and provide new insights into interventional strategies.
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To identify DEGs between HCC and adjacent normal tissues, R (version 3.5.1, Auckland, New Zealand) was used to apply significance analysis of microarray with limma version 3.34.8 (http://www.bioconductor.org/packages/release/bioc/html/limma.html) package25 in these three GEO datasets consisting of GSE57957, GSE64041, and GSE76427.
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sections[5] "Identification of differential expression genes" paragraph 2
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To identify DEGs between HCC and adjacent normal tissues, R (version 3.5.1, Auckland, New Zealand) was used to apply significance analysis of microarray with limma version 3.34.8 (http://www.bioconductor.org/packages/release/bioc/html/limma.html) package25 in these three GEO datasets consisting of GSE57957, GSE64041, and GSE76427.
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Three mRNA expression datasets were downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/), with the accession number of GSE57957, GSE64041, and GSE76427, including 37, 60, and 52 paired HCC tissue samples, respectively, used for discovering DEGs.
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sections[4] "Data study" paragraph 2
quote
Three mRNA expression datasets were downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/), with the accession number of GSE57957, GSE64041, and GSE76427, including 37, 60, and 52 paired HCC tissue samples, respectively, used for discovering DEGs.
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Three mRNA expression datasets were downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/), with the accession number of GSE57957, GSE64041, and GSE76427, including 37, 60, and 52 paired HCC tissue samples, respectively, used for discovering DEGs.
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Three mRNA expression datasets were downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/), with the accession number of GSE57957, GSE64041, and GSE76427, including 37, 60, and 52 paired HCC tissue samples, respectively, used for discovering DEGs.
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488
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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
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licence_read
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[2] object · 15 fields
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data:geo:GSE57957
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null
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Three mRNA expression datasets were downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/), with the accession number of GSE57957, GSE64041, and GSE76427, including 37, 60, and 52 paired HCC tissue samples, respectively, used for discovering DEGs.
structure object · 15 fields
repository
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GEO accession URL
access_statement_verbatim
Three mRNA expression datasets were downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/), with the accession number of GSE57957, GSE64041, and GSE76427, including 37, 60, and 52 paired HCC tissue samples, respectively, used for discovering DEGs.
access_statement_kind
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sample_count
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null
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null
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10558
taxon
Homo sapiens
title
Expression profile of Hepatocellular Carcinoma
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
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false
licence_read
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[3] object · 15 fields
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data:geo:GSE64041
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null
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Three mRNA expression datasets were downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/), with the accession number of GSE57957, GSE64041, and GSE76427, including 37, 60, and 52 paired HCC tissue samples, respectively, used for discovering DEGs.
structure object · 15 fields
repository
GEO
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GEO accession URL
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Three mRNA expression datasets were downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/), with the accession number of GSE57957, GSE64041, and GSE76427, including 37, 60, and 52 paired HCC tissue samples, respectively, used for discovering DEGs.
access_statement_kind
repository_route_statement
sample_accessions array · 125 items
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[124]
GSM2052579
sample_count
125
group_sizes
null
group_sizes_basis
null
platform
6244
taxon
Homo sapiens
title
Gene expression profiling in paired human hepatocellular carcinoma and liver parenchyma biopsies and normal liver biopsies.
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:GSE76427
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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=GSE76427
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null
access
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null
note
Three mRNA expression datasets were downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/), with the accession number of GSE57957, GSE64041, and GSE76427, including 37, 60, and 52 paired HCC tissue samples, respectively, used for discovering DEGs.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
Three mRNA expression datasets were downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/), with the accession number of GSE57957, GSE64041, and GSE76427, including 37, 60, and 52 paired HCC tissue samples, respectively, used for discovering DEGs.
access_statement_kind
repository_route_statement
sample_accessions array · 167 items
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[1]
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[166]
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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
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[5] object · 16 fields
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asset:table:pmid:30538557:1
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table
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jats-table
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sha256:359d77e4d2d41cca1d702cce5325f06ca8a5c17bf1b73600ff76d59b4e03efe5
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verified
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section[24]/table-wrap[1]#ts1-cmar-10-6079
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null
note
The sequence of PCR primers
structure object · 5 fields
pmcid
PMC6252784
section_index
24
section_title
Supplementary materials
row_count
6
column_count
3
table object · 8 fields
label
Table S1
caption
The sequence of PCR primers
rows array · 6 items
[0] array · 3 items
[0]
Gene
[1]
Forward 5′-3′
[2]
Reverse 5′-3′
[1] array · 3 items
[0]
Human GAPDH
[1]
GGAGCCAAAAGGGTCATCACTC
[2]
GAGGGGCCATCCACAGTCTTCT
[2] array · 3 items
[0]
Human SPINK1
[1]
TCTATCTGGTAACACTGGAGCTG
[2]
ACACGCATTCATTGGGATAAGT
[3] array · 3 items
[0]
Human TXNRD1
[1]
ATATGGCAAGAAGGTGATGGTCC
[2]
GGGCTTGTCCTAACAAAGCTG
[4] array · 3 items
[0]
Human LCAT
[1]
ACCTGGTCAACAATGGCTACG
[2]
TAGAGCAAGTGTAGACAGCCG
[5] array · 3 items
[0]
Human PZP
[1]
GGAGAAGGACTTATTCCACTGTG
[2]
ATCTTGCGTAGGCCCCTTTAT
locator
section[24]/table-wrap[1]#ts1-cmar-10-6079
gaps array · 8 items
[0]
asset:data:geo:GSE14520 not downloaded
[1]
asset:data:geo:GSE14520 licence not read
[2]
asset:data:geo:GSE57957 not downloaded
[3]
asset:data:geo:GSE57957 licence not read
[4]
asset:data:geo:GSE64041 not downloaded
[5]
asset:data:geo:GSE64041 licence not read
[6]
asset:data:geo:GSE76427 not downloaded
[7]
asset:data:geo:GSE76427 licence not read
analysis object · 4 fields
state
partial
methods array · 4 items
[0] object · 10 fields
id
method-1
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differential_expression
specific
limma_voom
label
Differential expression analysis
dsl_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
score
1
band
verbatim
quote
To identify DEGs between HCC and adjacent normal tissues, R (version 3.5.1, Auckland, New Zealand) was used to apply significance analysis of microarray with limma version 3.34.8 (http://www.bioconductor.org/packages/release/bioc/html/limma.html) package25 in these three GEO datasets consisting of GSE57957, GSE64041, and GSE76427.
[1] object · 10 fields
id
method-2
family
survival_analysis
specific
cox_proportional_hazards
label
Survival analysis
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[0]
cox_ph
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.7
band
medium
quote
Cox proportional hazards
[2] object · 10 fields
id
method-3
family
survival_analysis
specific
log_rank_test
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Survival analysis
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[0]
logrank_test
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
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high
quote
log-rank
[3] object · 10 fields
id
method-4
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network_analysis
specific
ppi_network
label
Network / pathway analysis
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[0]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.7
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medium
quote
protein-protein interaction
targets array · 0 items
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 · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
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: limma_voom.
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 · 4 items
[0]
GSE57957
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GSE76427
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GSE14520
resolved_accessions array · 4 items
[0]
GSE57957
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GSE64041
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GSE76427
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GSE14520
statements array · 1 item
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Three mRNA expression datasets were downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/), with the accession number of GSE57957, GSE64041, and GSE76427, including 37, 60, and 52 paired HCC tissue samples, respectively, used for discovering DEGs.
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The paper names GSE57957, GSE64041, GSE76427, GSE14520 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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To identify DEGs between HCC and adjacent normal tissues, R (version 3.5.1, Auckland, New Zealand) was used to apply significance analysis of microarray with limma version 3.34.8 (http://www.bioconductor.org/packages/release/bioc/html/limma.html) package25 in these three GEO datasets consisting of GSE57957, GSE64041, and GSE76427.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30538557", "kind": "science-record", "revision": 9, "content_hash": "sha256:9badbf677a1efb2fcf6ebcc7407e2abe054871d845f2b1b967e344b8a5f56d5f", "created_at": "2026-11-01T15:40:39Z", "updated_at": "2026-11-01T22:43:39Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Large-scale analysis reveals a novel risk score to predict overall survival in hepatocellular carcinoma.", "doi": "10.2147/CMAR.S181396", "pmid": "30538557", "authors": ["Yujia Zheng", "Yulin Liu", "Songfeng Zhao", "Zhetian Zheng", "Chunyi Shen", "Li An", "Yongliang Yuan"], "journal": "Cancer management and research", "year": 2018, "abstract": "BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality and an increasing incidence worldwide; however, there are very few effective diagnostic approaches and prognostic biomarkers.\nMATERIALS AND METHODS: One hundred forty-nine pairs of HCC samples from Gene Expression Omnibus (GEO) were obtained to screen differentially expressed genes (DEGs) between HCC and normal samples. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene ontology enrichment analyses, and protein-protein interaction network were used. Cox proportional hazards regression analysis was used to identify significant prognostic DEGs, with which a gene expression signature prognostic prediction model was identified in The Cancer Genome Atlas (TCGA) project discovery cohort. The robustness of this panel was assessed in the GSE14520 cohort. We verified details of the gene expression level of the key molecules through TCGA, GEO, and qPCR and used immunohistochemistry for substantiation in HCC tissues. The methylation states of these genes were also explored.\nRESULTS: Ninety-eight genes, consisting of 13 upregulated and 85 downregulated genes, were screened out in three datasets. KEGG and Gene ontology analysis for the DEGs revealed important biological features of each subtype. Protein-protein interaction network analysis was constructed, consisting of 64 nodes and 115 edges. A subset of four genes (SPINK1, TXNRD1, LCAT, and PZP) that formed a prognostic gene expression signature was established from TCGA and validated in GSE14520. Next, the expression details of the four genes were validated with TCGA, GEO, and clinical samples. The expression panels of the four genes were closely related to methylation states.\nCONCLUSION: This study identified a novel four-gene signature biomarker for predicting the prognosis of HCC. The biomarkers may also reveal molecular mechanisms underlying development of the disease and provide new insights into interventional strategies.", "claims": [{"id": "claim-method", "statement": "To identify DEGs between HCC and adjacent normal tissues, R (version 3.5.1, Auckland, New Zealand) was used to apply significance analysis of microarray with limma version 3.34.8 (http://www.bioconductor.org/packages/release/bioc/html/limma.html) package25 in these three GEO datasets consisting of GSE57957, GSE64041, and GSE76427.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30538557", "locator": "sections[5] \"Identification of differential expression genes\" paragraph 2", "quote": "To identify DEGs between HCC and adjacent normal tissues, R (version 3.5.1, Auckland, New Zealand) was used to apply significance analysis of microarray with limma version 3.34.8 (http://www.bioconductor.org/packages/release/bioc/html/limma.html) package25 in these three GEO datasets consisting of GSE57957, GSE64041, and GSE76427."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Three mRNA expression datasets were downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/), with the accession number of GSE57957, GSE64041, and GSE76427, including 37, 60, and 52 paired HCC tissue samples, respectively, used for discovering DEGs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30538557", "locator": "sections[4] \"Data study\" paragraph 2", "quote": "Three mRNA expression datasets were downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/), with the accession number of GSE57957, GSE64041, and GSE76427, including 37, 60, and 52 paired HCC tissue samples, respectively, used for discovering DEGs."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:30538557"], "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. 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