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pmid:36437949

Integrative multiomics evaluation reveals the importance of pseudouridine synthases in hepatocellular carcinoma.

Zhipeng Jin · Mengying Song · Jianping Wang · Wenjing Zhu · Dongxu Sun · Huayuan Liu · Guangjun Shi

Frontiers in genetics · 2022 doi:10.3389/fgene.2022.944681

Paper

complete

Experiment

complete

Data

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pmid:36437949
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2026-11-01T19:00:54Z
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title
Integrative multiomics evaluation reveals the importance of pseudouridine synthases in hepatocellular carcinoma.
doi
10.3389/fgene.2022.944681
pmid
36437949
authors array · 7 items
[0]
Zhipeng Jin
[1]
Mengying Song
[2]
Jianping Wang
[3]
Wenjing Zhu
[4]
Dongxu Sun
[5]
Huayuan Liu
[6]
Guangjun Shi
journal
Frontiers in genetics
year
2022
abstract
Background: The pseudouridine synthases (PUSs) have been reported to be associated with cancers. However, their involvement in hepatocellular carcinoma (HCC) has not been well documented. Here, we assess the roles of PUSs in HCC. Methods: RNA sequencing data of TCGA-LIHC and LIRI-JP were downloaded from the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), respectively. GSE36376 gene expression microarray was downloaded from the Gene Expression Omnibus (GEO). Proteomics data for an HBV-related HCC cohort was obtained from the CPTAC Data Portal. The RT-qPCR assay was performed to measure the relative mRNA expression of genes in clinical tissues and cell lines. Diagnostic efficiency was evaluated by the ROC curve. Prognostic value was assessed using the Kaplan-Meier curve, Cox regression model, and time-dependent ROC curve. Copy number variation (CNV) was analyzed using the GSCA database. Functional analysis was carried out with GSEA, GSVA, and clusterProfiler package. The tumor microenvironment (TME) related analysis was performed using ssGSEA and the ESTIMATE algorithm. Results: We identified 7 PUSs that were significantly upregulated in HCC, and 5 of them (DKC1, PUS1, PUS7, PUSL1, and RPUSD3) were independent risk factors for patients' OS. Meanwhile, the protein expression of DKC1, PUS1, and PUS7 was also upregulated and related to poor survival. Both mRNA and protein of these PUSs were highly diagnostic of HCC. Moreover, the CNV of PUS1, PUS7, PUS7L, and RPUSD2 was also associated with prognosis. Further functional analysis revealed that PUSs were mainly involved in pathways such as genetic information processing, substance metabolism, cell cycle, and immune regulation. Conclusion: PUSs may play crucial roles in HCC and could be used as potential biomarkers for the diagnosis and prognosis of patients.
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Prognostic value was assessed using the Kaplan-Meier curve, Cox regression model, and time-dependent ROC curve.
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
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Seven PUSs were significantly upregulated in HCC, and five of them were independent risk factors for overall survival.
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We identified 7 PUSs that were significantly upregulated in HCC, and 5 of them (DKC1, PUS1, PUS7, PUSL1, and RPUSD3) were independent risk factors for patients’ OS.
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Seven PUSs were significantly upregulated in HCC, and five of them were independent risk factors for overall survival.
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data_shapes array · 1 item
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evidence object · 3 fields
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0.8
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high
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Wilcoxon
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method-3
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survival_analysis
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cox_proportional_hazards
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Survival analysis
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[0]
cox_ph
missing_operations array · 0 items
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data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
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0.7
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Cox regression
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method-4
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survival_analysis
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log_rank_test
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Survival analysis
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[0]
logrank_test
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data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
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0.8
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log-rank
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id
method-5
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correlation_analysis
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spearman
label
Correlation analysis
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[0]
spearman_rho
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data_shapes array · 1 item
[0]
paired_numeric_columns
evidence object · 3 fields
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0.8
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high
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method-6
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diagnostic_evaluation
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roc
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confusion_counts
[1]
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[2]
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[3]
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[4]
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[5]
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missing_operations array · 0 items
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reference_standard_and_test
evidence object · 3 fields
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0.7
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ROC curve
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gaps array · 1 item
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method.reader_differs_from_extractor
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
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Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
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survival_analysis
[3]
statistical_regression
[4]
pca
[5]
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[6]
network_analysis
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differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
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complete
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R1
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nothing:replicable_now
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method object · 5 fields
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true
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survival_km
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: kaplan_meier.
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
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accessions array · 1 item
[0]
GSE36376
resolved_accessions array · 1 item
[0]
GSE36376
statements array · 1 item
[0]
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
basis
The paper names GSE36376 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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survival_km
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[0]
source:pmid:36437949
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data:geo:GSE36376
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run_analysis
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data:geo:GSE36376
gaps array · 0 items
review object · 5 fields
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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
2026-11-01T18:17:01Z
independence
single_reader
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method
verbatim
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verbatim
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5
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13358
completion_tokens
2598
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264
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[0] object · 4 fields
id
extraction
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review.independent_reader
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execution object · 5 fields
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absent
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not_run
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provenance object · 7 fields
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pmid:36437949
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paper
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pmid:36437949
[1] object · 3 fields
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source:pmid:36437949
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manuscript
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PMID 36437949 full text
[2] object · 3 fields
id
data:geo:GSE36376
type
dataset
label
GEO GSE36376
activities array · 3 items
[0] object · 4 fields
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activity-reading-sci-2026-11-01
type
classification
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[0] object · 3 fields
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pmid:36437949
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paper
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pmid:36437949
[1] object · 3 fields
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source:pmid:36437949
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manuscript
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PMID 36437949 full text
[2] object · 3 fields
id
data:geo:GSE36376
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dataset
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GEO GSE36376
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agent:corpus-assay-engine
[1] object · 4 fields
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activity-read-36437949
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extraction
used array · 1 item
[0]
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agent:minimax-reader
[2] object · 4 fields
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activity-resolve-GSE36376
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accession_resolution
used array · 1 item
[0]
data:geo:GSE36376
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agent:corpus-assay-engine
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agent:corpus-assay-engine
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agent:minimax-reader
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software
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dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
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lineage object · 4 fields
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pmid:36437949
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sha256:9391cbb40209f48574ce420e70cce8ae6e8c9400900128813b76380ae32f1407
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null
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[0]
asset:data:geo:GSE36376 licence not read
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asset:data:geo:GSE36376 not downloaded
[2]
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[3]
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[4]
review.human_critique
[5]
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[6]
review.machine_critique
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[0] object · 11 fields
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data_generation
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99e1195c7d6f
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99e1195c7d6f
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0.93
evidence array · 1 item
[0]
we assess the roles of PUSs in HCC. Methods: RNA sequencing data of TCGA-LIHC and LIRI-JP were downloade
order_basis
paper_text_order:307
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assay:1
[1] object · 11 fields
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data_generation
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99e1195c7d6f
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was obtained from the CPTAC Data Portal. The RT-qPCR assay was performed to measure the relative
[1]
obtained from the CPTAC Data Portal. The RT-qPCR assay was performed to measure the relative
[2]
PLEMENTARY TABLE S2Primer sequences used for RT-qPCR. SUPPLEMENTARY TABLE S3Results of differenti
[3]
MENTARY TABLE S2Primer sequences used for RT-qPCR. SUPPLEMENTARY TABLE S3Results of differenti
order_basis
paper_text_order:655
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Cell Bank (Shanghai, China). The cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM; Hy
order_basis
paper_text_order:2215
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assay:3
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f2132e96ae6c7a4e
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Prognostic value was assessed using the Kaplan-Meier curve, Cox regression model, and time-dependent ROC curve.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36437949", "kind": "science-record", "revision": 4, "content_hash": "sha256:4da2b81a14daae507f23634bfd79d0fb47612cb8e8819f7693a7fb4b44a9b8dc", "created_at": "2026-11-01T19:00:54Z", "updated_at": "2026-11-01T22:50:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrative multiomics evaluation reveals the importance of pseudouridine synthases in hepatocellular carcinoma.", "doi": "10.3389/fgene.2022.944681", "pmid": "36437949", "authors": ["Zhipeng Jin", "Mengying Song", "Jianping Wang", "Wenjing Zhu", "Dongxu Sun", "Huayuan Liu", "Guangjun Shi"], "journal": "Frontiers in genetics", "year": 2022, "abstract": "Background: The pseudouridine synthases (PUSs) have been reported to be associated with cancers. However, their involvement in hepatocellular carcinoma (HCC) has not been well documented. Here, we assess the roles of PUSs in HCC. Methods: RNA sequencing data of TCGA-LIHC and LIRI-JP were downloaded from the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), respectively. GSE36376 gene expression microarray was downloaded from the Gene Expression Omnibus (GEO). Proteomics data for an HBV-related HCC cohort was obtained from the CPTAC Data Portal. The RT-qPCR assay was performed to measure the relative mRNA expression of genes in clinical tissues and cell lines. Diagnostic efficiency was evaluated by the ROC curve. Prognostic value was assessed using the Kaplan-Meier curve, Cox regression model, and time-dependent ROC curve. Copy number variation (CNV) was analyzed using the GSCA database. Functional analysis was carried out with GSEA, GSVA, and clusterProfiler package. The tumor microenvironment (TME) related analysis was performed using ssGSEA and the ESTIMATE algorithm. Results: We identified 7 PUSs that were significantly upregulated in HCC, and 5 of them (DKC1, PUS1, PUS7, PUSL1, and RPUSD3) were independent risk factors for patients' OS. Meanwhile, the protein expression of DKC1, PUS1, and PUS7 was also upregulated and related to poor survival. Both mRNA and protein of these PUSs were highly diagnostic of HCC. Moreover, the CNV of PUS1, PUS7, PUS7L, and RPUSD2 was also associated with prognosis. Further functional analysis revealed that PUSs were mainly involved in pathways such as genetic information processing, substance metabolism, cell cycle, and immune regulation. Conclusion: PUSs may play crucial roles in HCC and could be used as potential biomarkers for the diagnosis and prognosis of patients.", "claims": [{"id": "claim-method", "statement": "Prognostic value was assessed using the Kaplan-Meier curve, Cox regression model, and time-dependent ROC curve.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36437949", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Prognostic value was assessed using the Kaplan-Meier curve, Cox regression model, and time-dependent ROC curve."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36437949", "locator": "sections[24] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Seven PUSs were significantly upregulated in HCC, and five of them were independent risk factors for overall survival.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36437949", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We identified 7 PUSs that were significantly upregulated in HCC, and 5 of them (DKC1, PUS1, PUS7, PUSL1, and RPUSD3) were independent risk factors for patients’ OS."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Seven PUSs were significantly upregulated in HCC, and five of them were independent risk factors for overall survival.", "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:36437949"], "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:GSE36376"], "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:GSE36376"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36437949", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2022.944681", "sha256": "sha256:dc58f012e83da648b321367c282edab361f75ade8f2042810256d99cf72c8e4b", "bytes": 47906, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2022.944681", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9686406", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE36376", "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=GSE36376", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE36376", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. 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