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pmid:35992857
Integrated multi-omics analysis identifies ENY2 as a predictor of recurrence and a regulator of telomere maintenance in hepatocellular carcinoma.
Jian-Hua Li · Yi-Feng Tao · Cong-Huan Shen · Rui-Dong Li · Zheng Wang · Hao Xing · En-Si Ma · Hong-Yuan Xue · Quan-Bao Zhang · Zhen-Yu Ma · Zheng-Xin Wang
Frontiers in oncology · 2022 doi:10.3389/fonc.2022.939948
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Accurate prediction of recurrence risk is urgently required for tailoring personalized treatment programs for individual HCC patients in advance. In this study, we analyzed a gene expression dataset from an HCC cohort with 247 samples and identified five genes including ENY2, GPAA1, NDUFA4L2, NEDD9, and NRP1 as the variables for the prediction of HCC recurrence, especially the early recurrence. The Cox model and risks score were validated in two public HCC cohorts (GSE76427 and The Cancer Genome Atlas (TCGA)) and one cohort from Huashan Hospital, which included a total of 641 samples. Moreover, the multivariate Cox regression analysis revealed that the risk score could serve as an independent prognostic factor in the prediction of HCC recurrence. In addition, we found that ENY2, GPAA1, and NDUFA4L2 were significantly upregulated in HCC of the two validation cohorts, and ENY2 had significantly higher expression levels than another four genes in malignant cells, suggesting that ENY2 might play key roles in malignant cells. The cell line analysis revealed that ENY2 could promote cell cycle progression, cell proliferation, migration, and invasion. The functional analysis of the genes correlated with ENY2 revealed that ENY2 might be involved in telomere maintenance, one of the fundamental hallmarks of cancer. 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downloaded", "asset:data:geo:GSE125449 licence not read", "asset:data:geo:GSE14520 not downloaded", "asset:data:geo:GSE14520 licence not read", "asset:data:geo:GSE76427 not downloaded", "asset:data:geo:GSE76427 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The Cox model was built by the R survival package (20)."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-3", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "analysis of variance"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "capability": {"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": {"tier": "R1", "reachable": true, "accessions": ["GSE14520", "GSE76427", "GSE125449"], "resolved_accessions": ["GSE14520", "GSE76427", "GSE125449"], "statements": ["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 GSE14520, GSE76427, GSE125449 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:35992857", "data:geo:GSE125449"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE125449"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:01:23Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9647, "completion_tokens": 2049, "cached_tokens": 128}}, "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:35992857", "type": "paper", "label": "pmid:35992857"}, {"id": "source:pmid:35992857", "type": "manuscript", "label": "PMID 35992857 full text"}, {"id": "data:geo:GSE125449", "type": "dataset", "label": "GEO GSE125449"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35992857", "type": "paper", "label": "pmid:35992857"}, {"id": "source:pmid:35992857", "type": "manuscript", "label": "PMID 35992857 full text"}, {"id": "data:geo:GSE125449", "type": "dataset", "label": "GEO GSE125449"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35992857", "type": "extraction", "used": ["source:pmid:35992857"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE125449", "type": "accession_resolution", "used": ["data:geo:GSE125449"], "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:35992857", "parent_hash": "sha256:f3737fa8147eb2bde87b3ca6e450f86988bf8d357f2b4c9b1c793e01351f97dc", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE125449 licence not read", "asset:data:geo:GSE125449 not downloaded", "asset:data:geo:GSE14520 licence not read", "asset:data:geo:GSE14520 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": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Materials and methods Cell culture and transfection The Roswell Park Memorial Institute (RPMI)-1", "were incubated at 37°C with 5% CO2. For cell transfection, the shRNA especially binding ENY2 RNA (shRN", "na). The cells in the logarithmic phase were transfected by Lipofectamine 2000 (Thermo Fisher Scienti", "37°C with 5% CO2. For cell transfection, the shRNA especially binding ENY2 RNA (shRNA 1-3, ENY2"], "order_basis": "paper_text_order:1708", "id": "assay:1"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The Cox model was built by the R survival package (20)."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}