Exploration and validation of a combined Hypoxia and m6A/m5C/m1A regulated gene signature for prognosis prediction of liver cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38097948", "kind": "science-record", "revision": 4, "content_hash": "sha256:31dd52c56d8eb43c55fb2a39b403b4373b90ada185f13cbc3eafffcd97fa9529", "created_at": "2026-11-01T19:03:02Z", "updated_at": "2026-11-01T22:10:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploration and validation of a combined Hypoxia and m6A/m5C/m1A regulated gene signature for prognosis prediction of liver cancer.", "doi": "10.1186/s12864-023-09876-3", "pmid": "38097948", "authors": ["Min Ren", "Bei Fan", "Guangcai Cao", "Rongrong Zong", "Liaoliao Feng", "Huiru Sun"], "journal": "BMC genomics", "year": 2023, "abstract": "BACKGROUND: It is widely acknowledged that hypoxia and m6A/m5C/m1A RNA modifications promote the occurrence and development of tumors by regulating the tumor microenvironment. This study aimed to establish a novel liver cancer risk signature based on hypoxia and m6A/m5C/m1A modifications.\nMETHODS: We collected data from The Cancer Genome Atlas (TCGA-LIHC), the National Omics Data Encyclopedia (NODE-HCC), the International Cancer Genome Consortium (ICGC), and the Gene Expression Omnibus (GEO) databases for our study (GSE59729, GSE41666). Using Cox regression and least absolute shrinkage and selection operator (LASSO) method, we developed a risk signature for liver cancer based on differentially expressed genes related to hypoxia and genes regulated by m6A/m5C/m1A modifications. We stratified patients into high- and low-risk groups and assessed differences between these groups in terms of gene mutations, copy number variations, pathway enrichment, stemness scores, immune infiltration, and predictive capabilities of the model for immunotherapy and chemotherapy efficacy.\nRESULTS: Our analysis revealed a significantly correlated between hypoxia and methylation as well as m6A/m5C/m1A RNA methylation. The three-gene prognosis signature (CEP55, DPH2, SMS) combining hypoxia and m6A/m5C/m1A regulated genes exhibited strong predictive performance in TCGA-LIHC, NODE-HCC, and ICGC-LIHC-JP cohorts. The low-risk group demonstrated a significantly better overall survival compared to the high-risk group (p < 0.0001 in TCGA, p = 0.0043 in NODE, p = 0.0015 in ICGC). The area under the curve (AUC) values for survival at 1, 2, and 3 years are all greater than 0.65 in the three cohorts. Univariate and Multivariate Cox regression analyses of the three datasets indicated that the signature could serve as an independent prognostic predictor (p < 0.001 in the three cohorts). The high-risk group exhibited more genome changes and higher homologous recombination deficiency scores and stemness scores. Analysis of immune infiltration and immune activation confirmed that the signature was associated with various immune microenvironment characteristics. Finally, patients in the high-risk group experienced a more favorable response to immunotherapy, and various common chemotherapy drugs.\nCONCLUSION: Our prognostic signature which integrates hypoxia and m6A/m5C/m1A-regulated genes, provides valuable insights for clinical prediction and treatment guidance for liver cancer patients.", "claims": [{"id": "claim-method", "statement": "Using Cox regression and least absolute shrinkage and selection operator (LASSO) method, we developed a risk signature for liver cancer based on differentially expressed genes related to hypoxia and genes regulated by m6A/m5C/m1A modifications.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38097948", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Using Cox regression and least absolute shrinkage and selection operator (LASSO) method, we developed a risk signature for liver cancer based on differentially expressed genes related to hypoxia and genes regulated by m6A/m5C/m1A modifications."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplement Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38097948", "locator": "sections[26] \"Availability of data and materials\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplement Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The three-gene HMRs prognostic signature separated patients by overall survival, achieved 1-, 2-, and 3-year survival AUC values greater than 0.65 in three cohorts, and independently predicted liver cancer prognosis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38097948", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The low-risk group demonstrated a significantly better overall survival compared to the high-risk group (p < 0.0001 in TCGA, p = 0.0043 in NODE, p = 0.0015 in ICGC)."}, {"asset": "source:pmid:38097948", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The area under the curve (AUC) values for survival at 1, 2, and 3 years are all greater than 0.65 in the three cohorts."}, {"asset": "source:pmid:38097948", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Univariate and Multivariate Cox regression analyses of the three datasets indicated that the signature could serve as an independent prognostic predictor (p < 0.001 in the three cohorts)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The three-gene HMRs prognostic signature separated patients by overall survival, achieved 1-, 2-, and 3-year survival AUC values greater than 0.65 in three cohorts, and independently predicted liver cancer prognosis.", "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:38097948"], "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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