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pmid:36866237

Novel Gene Signatures Promote Epithelial-Mesenchymal Transition (EMT) in Glucose Deprivation-Based Microenvironment to Predict Recurrence-Free Survival in Hepatocellular Carcinoma.

Yuan Huang · Shi-Rong Li · Ying-Jie Gao · Yan-Hua Zhu · Xiao-Feng Zhang

Journal of oncology · 2023 doi:10.1155/2023/6114976

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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2026-11-01T19:01:30Z
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title
Novel Gene Signatures Promote Epithelial-Mesenchymal Transition (EMT) in Glucose Deprivation-Based Microenvironment to Predict Recurrence-Free Survival in Hepatocellular Carcinoma.
doi
10.1155/2023/6114976
pmid
36866237
authors array · 5 items
[0]
Yuan Huang
[1]
Shi-Rong Li
[2]
Ying-Jie Gao
[3]
Yan-Hua Zhu
[4]
Xiao-Feng Zhang
journal
Journal of oncology
year
2023
abstract
Background: Current research studies have suggested that glucose deprivation (GD)-based tumor microenvironment (TME) can promote epithelial-mesenchymal transition (EMT) of tumor cells, leading to tumor invasion and metastasis. However, no one has yet studied detailedly the synthetic studies that include GD features in TME with EMT status. In our research, we comprehensively developed and validated a robust signature regarding GD and EMT status to provide prognostic value for patients with liver cancer. Methods: GD and EMT status were estimated with transcriptomic profiles based on WGCNA and t-SNE algorithms. Two cohorts of training (TCGA_LIHC) and validation (GSE76427) datasets were analyzed with the Cox regression and logistic regression analyses. We identified a 2-mRNA signature to establish a GD-EMT-based gene risk model for the prediction of HCC relapse. Results: Patients with significant GD-EMT status were divided into two subgroups: GDlow/EMTlow and GDhigh/EMThigh, with the latter having significantly worse recurrence-free survival (P < 0.01). We employed the least absolute shrinkage and selection operator (LASSO) technique as a method for HNF4A and SLC2A4 filtering and constructing a risk score for risk stratification. In the multivariate analysis, this risk score predicted recurrence-free survival (RFS) in both the discovery and validation cohorts and remained valid in patients stratified by TNM stage and age at diagnosis. The nomogram that combines risk score and TNM stage as well as age produces improved performance and net benefits in the analysis of calibration and decision curves in training and validation groups. Conclusions: The GD-EMT-based signature predictive model may provide a prognosis classifier for HCC patients with a high risk of postoperative recurrence to decrease the relapse rate.
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We identified a 2-mRNA signature to establish a GD-EMT-based gene risk model for the prediction of HCC relapse.
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We identified a 2-mRNA signature to establish a GD-EMT-based gene risk model for the prediction of HCC relapse.
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We identified a 2-mRNA signature to establish a GD-EMT-based gene risk model for the prediction of HCC relapse.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36866237", "kind": "science-record", "revision": 4, "content_hash": "sha256:2499f1265a5ce4ea4d786fe0cf2767721d483b5aa13e7e37f13c3ce744ca741a", "created_at": "2026-11-01T19:01:30Z", "updated_at": "2026-11-01T22:51:25Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Novel Gene Signatures Promote Epithelial-Mesenchymal Transition (EMT) in Glucose Deprivation-Based Microenvironment to Predict Recurrence-Free Survival in Hepatocellular Carcinoma.", "doi": "10.1155/2023/6114976", "pmid": "36866237", "authors": ["Yuan Huang", "Shi-Rong Li", "Ying-Jie Gao", "Yan-Hua Zhu", "Xiao-Feng Zhang"], "journal": "Journal of oncology", "year": 2023, "abstract": "Background: Current research studies have suggested that glucose deprivation (GD)-based tumor microenvironment (TME) can promote epithelial-mesenchymal transition (EMT) of tumor cells, leading to tumor invasion and metastasis. However, no one has yet studied detailedly the synthetic studies that include GD features in TME with EMT status. In our research, we comprehensively developed and validated a robust signature regarding GD and EMT status to provide prognostic value for patients with liver cancer.\nMethods: GD and EMT status were estimated with transcriptomic profiles based on WGCNA and t-SNE algorithms. Two cohorts of training (TCGA_LIHC) and validation (GSE76427) datasets were analyzed with the Cox regression and logistic regression analyses. We identified a 2-mRNA signature to establish a GD-EMT-based gene risk model for the prediction of HCC relapse.\nResults: Patients with significant GD-EMT status were divided into two subgroups: GDlow/EMTlow and GDhigh/EMThigh, with the latter having significantly worse recurrence-free survival (P < 0.01). We employed the least absolute shrinkage and selection operator (LASSO) technique as a method for HNF4A and SLC2A4 filtering and constructing a risk score for risk stratification. In the multivariate analysis, this risk score predicted recurrence-free survival (RFS) in both the discovery and validation cohorts and remained valid in patients stratified by TNM stage and age at diagnosis. The nomogram that combines risk score and TNM stage as well as age produces improved performance and net benefits in the analysis of calibration and decision curves in training and validation groups.\nConclusions: The GD-EMT-based signature predictive model may provide a prognosis classifier for HCC patients with a high risk of postoperative recurrence to decrease the relapse rate.", "claims": [{"id": "claim-method", "statement": "Two cohorts of training (TCGA_LIHC) and validation (GSE76427) datasets were analyzed with the Cox regression and logistic regression analyses.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36866237", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Two cohorts of training (TCGA_LIHC) and validation (GSE76427) datasets were analyzed with the Cox regression and logistic regression analyses."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The research data used to support the findings of this study are available. The database can be obtained from the corresponding author upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36866237", "locator": "sections[26] \"Data Availability\" paragraph 2", "quote": "The research data used to support the findings of this study are available. The database can be obtained from the corresponding author upon request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We identified a 2-mRNA signature to establish a GD-EMT-based gene risk model for the prediction of HCC relapse.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36866237", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "We identified a 2-mRNA signature to establish a GD-EMT-based gene risk model for the prediction of HCC relapse."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We identified a 2-mRNA signature to establish a GD-EMT-based gene risk model for the prediction of HCC relapse.", "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:36866237"], "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:GSE140867"], "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:GSE140867"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36866237", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2023/6114976", "sha256": "sha256:a978fcd87d0bde5b76e8b84b52b4c36a7f47ae6f35f7de7f8053d339a3c8673e", "bytes": 53865, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2023/6114976", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9974289", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE140867", "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=GSE140867", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE140867", "version": null, "note": "The research data used to support the findings of this study are available. The database can be obtained from the corresponding author upon request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The research data used to support the findings of this study are available. The database can be obtained from the corresponding author upon request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4189001", "GSM4189002", "GSM4189003", "GSM4189004", "GSM4189005", "GSM4189006", "GSM4189007", "GSM4189008"], "sample_count": 8, "group_sizes": null, "group_sizes_basis": null, "platform": "10332", "taxon": "Homo sapiens", "title": "Effects of glucose exposures on gene expressions in HepG2 cells", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"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": "The research data used to support the findings of this study are available. The database can be obtained from the corresponding author upon request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The research data used to support the findings of this study are available. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:36866237", "data:geo:GSE140867"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE140867"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:32:29Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 15448, "completion_tokens": 1421, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:36866237", "type": "paper", "label": "pmid:36866237"}, {"id": "source:pmid:36866237", "type": "manuscript", "label": "PMID 36866237 full text"}, {"id": "data:geo:GSE140867", "type": "dataset", "label": "GEO GSE140867"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36866237", "type": "paper", "label": "pmid:36866237"}, {"id": "source:pmid:36866237", "type": "manuscript", "label": "PMID 36866237 full text"}, {"id": "data:geo:GSE140867", "type": "dataset", "label": "GEO GSE140867"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36866237", "type": "extraction", "used": ["source:pmid:36866237"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE140867", "type": "accession_resolution", "used": ["data:geo:GSE140867"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"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": {"parent_id": "pmid:36866237", "parent_hash": "sha256:3f4282f06c97e59e63cfda351cca6b03190549f04b1a7fd733e071c219047e2a", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE140867 licence not read", "asset:data:geo:GSE140867 not downloaded", "asset:data:geo:GSE76427 licence not read", "asset:data:geo:GSE76427 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["llege (Chengdu, China). 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