Construction of novel lncRNA-miRNA-mRNA ceRNA networks associated with prognosis of hepatitis C virus related hepatocellular carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36217480", "kind": "science-record", "revision": 4, "content_hash": "sha256:89ebef9b1040b9bea9c8d3226a778e096a929c5d64a36adfd516ee3ad8594bae", "created_at": "2026-11-01T18:15:34Z", "updated_at": "2026-11-01T22:07:47Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Construction of novel lncRNA-miRNA-mRNA ceRNA networks associated with prognosis of hepatitis C virus related hepatocellular carcinoma.", "doi": "10.1016/j.heliyon.2022.e10832", "pmid": "36217480", "authors": ["Lishi Shao", "Lei Liang", "Qixiang Fang", "Jiaping Wang"], "journal": "Heliyon", "year": 2022, "abstract": "Background: Hepatitis C virus (HCV) infection contribute to liver fibrosis and cirrhosis, which significantly increases the risk of hepatocellular carcinoma (HCC) development. Previous studies have demonstrated the pivotal role of competitive endogenous RNA (ceRNA) networks in tumorigenesis and cancer progression. Consequently, we herein seek to identify and evaluate the prognostic relevance of a novel ceRNA network associated with HCV-related HCC.\nMethods: Differentially expressed genes (DEGs) in GSE140846 dataset from GEO were identified using Network Analyst, and GO, KEGG and Reactome analyses were performed. Furthermore, a protein-protein interaction network was generated, and hub genes were detected. Hub gene expression levels, as well as those of their upstream lncRNAs and miRNAs and associated survival analyses were conducted using appropriate bioinformatics databases. Predicted target relationships were used to establish putative ceRNA networks for HCV-related HCC.\nResults: A total of 372 and 360 up- and down-regulated DE-mRNA were identified, which were associated with nuclear division, cell cycle, and ATPase activity. A PPI network containing 704 DE-mRNAs was constructed, and the 6 hub gene with the highest degree of connectivity were selected for subsequent analysis. We discovered that 22 miRNAs and 4 lncRNAs upstream of 11 hub gene were significantly associated with poor prognosis of HCV-related HCC, and used them to constructe a prognostic ceRNA network. Further experiments confirmed the ceRNA-regulatory relationship of BUB1-hsa-miR-193a-3p-MALAT1.\nConclusion: This study provides novel insights into the lncRNA-miRNA-mRNA ceRNA network, and reveals potential lncRNA biomarkers in HCV related HCC.", "claims": [{"id": "claim-method", "statement": "Network Analyst (https://www.networkanalyst.ca/) was used to identify DE-mRNAs, DE-miRNAs, and DE-lncRNAs when comparing control and HCC patient samples in GSE140846 dataset, using adjusted P value <0.05 and absolute log2 fold change (FC) > 1 as cutoff criteria for significance.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36217480", "locator": "sections[3] \"Identification of differentially expressed genes (DEGs) in microarray data\" paragraph 2", "quote": "Network Analyst (https://www.networkanalyst.ca/) was used to identify DE-mRNAs, DE-miRNAs, and DE-lncRNAs when comparing control and HCC patient samples in GSE140846 dataset, using adjusted P value <0.05 and absolute log2 fold change (FC) > 1 as cutoff criteria for significance."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data included in article/supp. material/referenced in article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36217480", "locator": "sections[23] \"Data availability statement\" paragraph 2", "quote": "Data included in article/supp. material/referenced in article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Differential-expression analysis of GEO dataset GSE140846 identified 1,177 differentially expressed genes in HCV-related hepatocellular carcinoma, comprising 732 DE-mRNAs, 20 DE-miRNAs, and 215 DE-lncRNAs.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36217480", "locator": "sections[11] \"Identification of DEGs associated to HCV-related HCC\" paragraph 2", "quote": "In comparing samples from non-infected normal liver and HCV-related HCC tissue, a total of 1177 DEGs (697 up-regulated and 480 down-regulated expression) were identified, including 732 DE-mRNA (Figure 1A and Figure 1D), 20 DE-miRNA (Figure 1B and Figure 1E), and 215 DE-lncRNA (Figure 1C and Figure 1F)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Differential-expression analysis of GEO dataset GSE140846 identified 1,177 differentially expressed genes in HCV-related hepatocellular carcinoma, comprising 732 DE-mRNAs, 20 DE-miRNAs, and 215 DE-lncRNAs.", "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:36217480"], "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:GSE140846"], "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:GSE140846"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36217480", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.heliyon.2022.e10832", "sha256": "sha256:03450845be4be041f784597d4f93ac48a491aa30b76693993e1c695db113d0b5", "bytes": 43725, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.heliyon.2022.e10832", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9547242", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE140846", "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=GSE140846", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE140846", "version": null, "note": "Data included in article/supp. material/referenced in article.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data included in article/supp. material/referenced in article.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4160224", "GSM4160225", "GSM4160226", "GSM4160227", "GSM4160228", "GSM4160229", "GSM4188845", "GSM4188846", "GSM4188847", "GSM4188848", "GSM4188849", "GSM4188850", "GSM4188851", "GSM4188852", "GSM4188853", "GSM4188854"], "sample_count": 16, "group_sizes": null, "group_sizes_basis": null, "platform": "16791", "taxon": "Homo sapiens", "title": "Integrative analysis of microRNAs and mRNAs in liver tissue and exosomes from blood of hepatitis C virus (HCV) related hepatocellular carcinoma (HCC) patient to identify biomarker and regulators of HCC", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE140846 not downloaded", "asset:data:geo:GSE140846 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Kaplan-Meier"}}, {"id": "method-2", "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": 0.8, "band": "high", "quote": "Cox regression"}}, {"id": "method-3", "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": "protein-protein interaction"}}, {"id": "method-4", "family": null, "specific": null, "label": "Network Analyst differential-expression analysis using adjusted P value <0.05 and absolute log2 fold change >1 as significance cutoffs", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Network Analyst (https://www.networkanalyst.ca/) was used to identify DE-mRNAs, DE-miRNAs, and DE-lncRNAs when comparing control and HCC patient samples in GSE140846 dataset, using adjusted P value <0.05 and absolute log2 fold change (FC) > 1 as cutoff criteria for significance."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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