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pmid:34692847
Potential lncRNA Biomarkers for HBV-Related Hepatocellular Carcinoma Diagnosis Revealed by Analysis on Coexpression Network.
Shunqiang Nong · Xiaohao Chen · Zechen Wang · Guidan Xu · Wujun Wei · Bin Peng · Lü Zhou · Liuzhi Wei · Jingjie Zhao · Qiuju Wei · Yibin Deng · Lingzhang Meng
BioMed research international · 2021 doi:10.1155/2021/9972011
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Experiment
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Complete file
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The aim of the present study was to determine an lncRNA signature for the diagnosis of HBV-related HCC.\nMETHODS: HBV-related HCC expression profiles (GSE55092, GSE19665, and GSE84402) were abstracted from the GEO (Gene Expression Omnibus) data resource, and R package limma and RobustRankAggreg were employed to identify common differentially expressed genes (DEGs). Using machine learning, optimal diagnostic lncRNA molecular markers for HBV-related HCC were identified. The expression of candidate lncRNAs was cross-validated in GSE121248, and an ROC (receiver operating characteristic) curve of lncRNA biomarkers was carried out. Additionally, a coexpression network and functional annotation was built, after which a PPI (protein-protein interaction) network along with module analysis were conducted with the Cytoscape open source software.\nRESULT: A total of 38 DElncRNAs and 543 DEmRNAs were identified with a fold change larger than 2.0 and a P value < 0.05. By machine learning, AL356056.2, AL445524.1, TRIM52-AS1, AC093642.1, EHMT2-AS1, AC003991.1, AC008040.1, LINC00844, and LINC01018 were screened out as optional diagnostic lncRNA biosignatures for HBV-related HCC. The AUC (areas under the curve) of the SVM (support vector machine) model and random forest model were 0.957 and 0.904, respectively, and the specificity and sensitivity were 95.7 and 100% and 94.3 and 86.5%, respectively. The results of functional enrichment analysis showed that the integrated coexpressed DEmRNAs shared common cascades in the p53 signaling pathway, retinol metabolism, PI3K-Akt signaling cascade, and chemical carcinogenesis. The integrated DEmRNA PPI network complex was found to be comprised of 87 nodes, and two vital modules with a high degree were selected with the MCODE app.\nCONCLUSION: The present study identified nine potential diagnostic biomarkers for HBV-related HCC, all of which could potentially modulated gene expression related to inflammatory conditions in the tumor immune microenvironment. The functional annotation of the target DEmRNAs yielded novel evidence in evaluating the precise functions of lncRNA in HBV-related HCC.", "claims": [{"id": "claim-method", "statement": "The DElncRNAs along with the DEmRNAs between HBV-linked HCC and nontumor tissues were computed through the limma R package V3.5.2 in R software in each dataset. 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Afterwards, the RobustRankAggreg (RRA) R package was used to integrate and analyze the three gene lists that were subsequently sorted via the logFC value."}}, {"id": "method-2", "family": "machine_learning", "specific": "random_forest", "label": "Machine learning", "dsl_operations": [], "missing_operations": ["machine_learning_random_forest"], "expressible": false, "parameters": {"auc": "The AUC (areas under the curve)"}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.7, "band": "medium", "quote": "random forest"}}, {"id": "method-3", "family": "machine_learning", "specific": "support_vector_machine", "label": "Machine learning", "dsl_operations": ["train_classifier", "cross_validate", "roc_auc"], "missing_operations": [], "expressible": true, "parameters": {"auc": "The AUC (areas under the curve)"}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.7, "band": "medium", "quote": "SVM"}}, {"id": "method-4", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "PPI"}}], "targets": [], "gaps": []}, "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "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": ["GSE55092", "GSE19665", "GSE84402", "GSE121248"], "resolved_accessions": ["GSE55092", "GSE19665", "GSE84402", "GSE121248"], "statements": ["The datasets, as well as the code generated or analyzed in this work, can be accessed from the corresponding authors on reasonable request."], "basis": "The paper names GSE55092, GSE19665, GSE84402, GSE121248 in NCBI-GEO data resource and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:34692847", "data:geo:GSE121248"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE121248"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:04:56Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14391, "completion_tokens": 2108, "cached_tokens": 0}}, "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:34692847", "type": "paper", "label": "pmid:34692847"}, {"id": "source:pmid:34692847", "type": "manuscript", "label": "PMID 34692847 full text"}, {"id": "data:geo:GSE121248", "type": "dataset", "label": "GEO GSE121248"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34692847", "type": "paper", "label": "pmid:34692847"}, {"id": "source:pmid:34692847", "type": "manuscript", "label": "PMID 34692847 full text"}, {"id": "data:geo:GSE121248", "type": "dataset", "label": "GEO GSE121248"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34692847", "type": "extraction", "used": ["source:pmid:34692847"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE121248", "type": "accession_resolution", "used": ["data:geo:GSE121248"], "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:34692847", "parent_hash": "sha256:60ab9444623e59183faf9b7dfd9d033bde199d7af239bae3739abbef1f9c155b", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE121248 licence not read", "asset:data:geo:GSE121248 not downloaded", "asset:data:geo:GSE19665 licence not read", "asset:data:geo:GSE19665 not downloaded", "asset:data:geo:GSE55092 licence not read", "asset:data:geo:GSE55092 not downloaded", "asset:data:geo:GSE84402 licence not read", "asset:data:geo:GSE84402 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The DElncRNAs along with the DEmRNAs between HBV-linked HCC and nontumor tissues were computed through the limma R package V3.5.2 in R software in each dataset. Afterwards, the RobustRankAggreg (RRA) R package was used to integrate and analyze the three gene lists that were subsequently sorted via the logFC value."], "order_basis": "analysis_only", "id": "assay:1"}]}