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pmid:38054921

Development and evaluation of a risk score model based on a WNT score gene-associated signature for predicting the clinical outcome and the tumour microenvironment of hepatocellular carcinoma.

Penghui Li · Xiao Ma · Di Huang · Xinyu Gu

International journal of immunopathology and pharmacology · 2023 doi:10.1177/03946320231218179

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Experiment

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Data

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title
Development and evaluation of a risk score model based on a WNT score gene-associated signature for predicting the clinical outcome and the tumour microenvironment of hepatocellular carcinoma.
doi
10.1177/03946320231218179
pmid
38054921
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[0]
Penghui Li
[1]
Xiao Ma
[2]
Di Huang
[3]
Xinyu Gu
journal
International journal of immunopathology and pharmacology
year
2023
abstract
Background: Hepatocellular carcinoma (HCC) is currently one of the most life-threatening diseases worldwide. However, the factors, genes, and processes involved in the mechanisms of HCC initiation, development, and metastasis remain to be identified.Methods: WNT signalling pathways may play important roles in cancer initiation and progression. Thus, it would be informative to construct a WNT signature-based gene model for the prognosis of HCC and the prediction of therapeutic efficacy. We curated genomic profiles for HCC from The Cancer Genome Atlas (TCGA) and divided them into training and internal validation datasets. We also used samples from GSE14520 and HCCDB18 as validation datasets and clustered them by ConsensusClusterPlus analysis. We applied WebGestaltR to the WNT score-associated differentially expressed genes (DEGs) and conducted a signalling pathway enrichment analysis. We assessed the tumour immune microenvironment with ESTIMATE, Microenvironment Cell Populations (MCP)-counter, single-sample gene set enrichment analysis (ssGSEA), and tumour immune dysfunction and exclusion (TIDE).Results: We performed a least absolute shrinkage and selection operator (LASSO) regression analysis to identify the prognosis-related hub genes, identified the risk and protective factor genes associated with HCC, classified them into two clusters, and found that Cluster 2 had a significantly better prognosis than Cluster 1. Moreover, the latter had advanced clinical features compared with the former. Uridine-cytosine kinase 1 (UCK1), myristoylated alanine-rich C-kinase substrate-like protein 1 (MARCKSL1), P-antigen family member 1 (PAGE1), and killer cell lectin-like receptor B1 (KLRB1) were detected and used to construct a simplified prognostic model for HCC. The high risk score subgroup showed a poorer prognosis than the low risk score subgroup, and the model assessed HCC prognosis consistently and effectively.Conclusions: The WNT score-related gene-based model designed and evaluated herein had strong prognostic and predictive ability for HCC and could, therefore, facilitate decision-making in the prognosis and therapeutic efficacy assessment of HCC.
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We then used the glmnet package in R to perform a LASSO regression analysis and reduce the number of genes in the risk model.
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sections[21] "Prognostic target gene identification" paragraph 2
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We then used the glmnet package in R to perform a LASSO regression analysis and reduce the number of genes in the risk model.
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The Cancer Genome Atlas (TCGA) database (https://portal.gdc.cancer.gov/) and the liver hepatocellular carcinoma (LIHC) mRNA expression profiles with fragments per kilobase million (FPKM) values served as the training set.
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The Cancer Genome Atlas (TCGA) database (https://portal.gdc.cancer.gov/) and the liver hepatocellular carcinoma (LIHC) mRNA expression profiles with fragments per kilobase million (FPKM) values served as the training set.
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The high risk score subgroup showed a poorer prognosis than the low risk score subgroup.
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The high risk score subgroup showed a poorer prognosis than the low risk score subgroup, and the model assessed HCC prognosis consistently and effectively.
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The high risk score subgroup showed a poorer prognosis than the low risk score subgroup.
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488
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null
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null
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3921;571
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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
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[3] object · 15 fields
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data:geo:GSE91061
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE91061
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null
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The Cancer Genome Atlas (TCGA) database (https://portal.gdc.cancer.gov/) and the liver hepatocellular carcinoma (LIHC) mRNA expression profiles with fragments per kilobase million (FPKM) values served as the training set.
structure object · 15 fields
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GEO
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GEO accession URL
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The Cancer Genome Atlas (TCGA) database (https://portal.gdc.cancer.gov/) and the liver hepatocellular carcinoma (LIHC) mRNA expression profiles with fragments per kilobase million (FPKM) values served as the training set.
access_statement_kind
repository_route_statement
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109
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null
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null
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9052
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Homo sapiens
title
Molecular portraits of tumor mutational and micro-environmental sculpting by immune checkpoint blockade therapy
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2026-11-01T15:39:55Z
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identifier_resolution_only_no_download_no_licence_read
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false
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gaps array · 6 items
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analysis object · 4 fields
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[0] object · 10 fields
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differential_expression
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Network / pathway analysis
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pathway enrichment
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null
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LASSO regression
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score
1
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We then used the glmnet package in R to perform a LASSO regression analysis and reduce the number of genes in the risk model.
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capability object · 3 fields
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candidate
Automated Assays Laravel application and simulated adapters
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The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
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tier
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GSE91061
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[0]
The Cancer Genome Atlas (TCGA) database (https://portal.gdc.cancer.gov/) and the liver hepatocellular carcinoma (LIHC) mRNA expression profiles with fragments per kilobase million (FPKM) values served as the training set.
basis
The paper names GSE14520, GSE135222, GSE91061 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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MiniMax-M3.1-Flash
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minimax
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minimax
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extraction
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PMID 38054921 full text
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GEO GSE135222
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c profile data were removed. RNA sequencing (RNA-Seq) data were acquired for 203 samples from HCC
[1]
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38054921", "kind": "science-record", "revision": 3, "content_hash": "sha256:d0e6cbae5c97a56bca6e31daaaaac697dc0b540f9d5794af762f2434d0387508", "created_at": "2026-11-01T19:03:00Z", "updated_at": "2026-11-01T22:10:49Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Development and evaluation of a risk score model based on a WNT score gene-associated signature for predicting the clinical outcome and the tumour microenvironment of hepatocellular carcinoma.", "doi": "10.1177/03946320231218179", "pmid": "38054921", "authors": ["Penghui Li", "Xiao Ma", "Di Huang", "Xinyu Gu"], "journal": "International journal of immunopathology and pharmacology", "year": 2023, "abstract": "Background: Hepatocellular carcinoma (HCC) is currently one of the most life-threatening diseases worldwide. However, the factors, genes, and processes involved in the mechanisms of HCC initiation, development, and metastasis remain to be identified.Methods: WNT signalling pathways may play important roles in cancer initiation and progression. Thus, it would be informative to construct a WNT signature-based gene model for the prognosis of HCC and the prediction of therapeutic efficacy. We curated genomic profiles for HCC from The Cancer Genome Atlas (TCGA) and divided them into training and internal validation datasets. We also used samples from GSE14520 and HCCDB18 as validation datasets and clustered them by ConsensusClusterPlus analysis. We applied WebGestaltR to the WNT score-associated differentially expressed genes (DEGs) and conducted a signalling pathway enrichment analysis. We assessed the tumour immune microenvironment with ESTIMATE, Microenvironment Cell Populations (MCP)-counter, single-sample gene set enrichment analysis (ssGSEA), and tumour immune dysfunction and exclusion (TIDE).Results: We performed a least absolute shrinkage and selection operator (LASSO) regression analysis to identify the prognosis-related hub genes, identified the risk and protective factor genes associated with HCC, classified them into two clusters, and found that Cluster 2 had a significantly better prognosis than Cluster 1. Moreover, the latter had advanced clinical features compared with the former. Uridine-cytosine kinase 1 (UCK1), myristoylated alanine-rich C-kinase substrate-like protein 1 (MARCKSL1), P-antigen family member 1 (PAGE1), and killer cell lectin-like receptor B1 (KLRB1) were detected and used to construct a simplified prognostic model for HCC. The high risk score subgroup showed a poorer prognosis than the low risk score subgroup, and the model assessed HCC prognosis consistently and effectively.Conclusions: The WNT score-related gene-based model designed and evaluated herein had strong prognostic and predictive ability for HCC and could, therefore, facilitate decision-making in the prognosis and therapeutic efficacy assessment of HCC.", "claims": [{"id": "claim-method", "statement": "We then used the glmnet package in R to perform a LASSO regression analysis and reduce the number of genes in the risk model.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38054921", "locator": "sections[21] \"Prognostic target gene identification\" paragraph 2", "quote": "We then used the glmnet package in R to perform a LASSO regression analysis and reduce the number of genes in the risk model."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The Cancer Genome Atlas (TCGA) database (https://portal.gdc.cancer.gov/) and the liver hepatocellular carcinoma (LIHC) mRNA expression profiles with fragments per kilobase million (FPKM) values served as the training set.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38054921", "locator": "sections[3] \"Data collection\" paragraph 2", "quote": "The Cancer Genome Atlas (TCGA) database (https://portal.gdc.cancer.gov/) and the liver hepatocellular carcinoma (LIHC) mRNA expression profiles with fragments per kilobase million (FPKM) values served as the training set."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The high risk score subgroup showed a poorer prognosis than the low risk score subgroup.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38054921", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The high risk score subgroup showed a poorer prognosis than the low risk score subgroup, and the model assessed HCC prognosis consistently and effectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The high risk score subgroup showed a poorer prognosis than the low risk score subgroup.", "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:38054921"], "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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