High Squalene Epoxidase in Tumors Predicts Worse Survival in Patients With Hepatocellular Carcinoma: Integrated Bioinformatic Analysis on NAFLD and HCC.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32216563", "kind": "science-record", "revision": 8, "content_hash": "sha256:9f0d27d934dab30cc1c16faee40e9c7ac156b46d4a6913c0c485a4801fbe643f", "created_at": "2026-11-01T15:40:58Z", "updated_at": "2026-11-01T22:01:26Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "High Squalene Epoxidase in Tumors Predicts Worse Survival in Patients With Hepatocellular Carcinoma: Integrated Bioinformatic Analysis on NAFLD and HCC.", "doi": "10.1177/1073274820914663", "pmid": "32216563", "authors": ["Tingting Shen", "Yunfei Lu", "Qin Zhang"], "journal": "Cancer control : journal of the Moffitt Cancer Center", "year": 2020, "abstract": "This study aimed to identify candidate biomarkers for predicting outcomes in nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Using Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) databases, we identified common upregulated differential expressed genes (DEGs) in patients with NAFLD/nonalcoholic steatohepatitis (NASH) and HCC and conducted survival analysis of these upregulated DEGs with HCC outcomes. Two common upregulated DEGs including squalene epoxidase (SQLE) and EPPK1 messenger RNA (mRNA) were significantly upregulated in NAFLD, NASH, and HCC tissues, both in GSE45436 (P < .001) and TCGA profile (P < .001). Both SQLE and EPPK1 mRNA were upregulated in 15.56% and 8.06% patients with HCC in TCGA profile. Overexpression of SQLE in tumors was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in patients with HCC (log-rank P = .027 and log-rank P = .048, respectively), while no statistical significances of OS and DFS were found in EPPK1 groups (both log-rank P > .05). For validation, SQLE upregulation contributed to significantly worse OS in patients wih HCC using Kaplan-Meier plotter analysis (hazard ratio = 1.43, 95% confidence interval: 1.01-2.02, log-rank P = .043). In addition, high level of SQLE significantly associated with advanced neoplasm histologic grade, advanced AJCC stage, and α-fetoprotein elevation (P = .036, .045, and .029, respectively). Squalene epoxidase is associated with OS and DFS and serves as a novel prognostic biomarker for patients with HCC.", "claims": [{"id": "claim-method", "statement": "Liver Hepatocellular Carcinoma (The Cancer Genome Atlas [TCGA], Provisional) database in cBioPortal for cancer genomics web service was used for identifying potential candidate biomarkers for predicting the overall survival (OS) and disease-free survival (DFS) of patients with HCC. Additionally, the Kaplan-Meier plotter online service (http://kmplot.com/analysis/)19 was used for validation of candidates with auto select best cutoff and OS in patients with HCC.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32216563", "locator": "sections[5] \"Survival Analysis\" paragraph 2", "quote": "Liver Hepatocellular Carcinoma (The Cancer Genome Atlas [TCGA], Provisional) database in cBioPortal for cancer genomics web service was used for identifying potential candidate biomarkers for predicting the overall survival (OS) and disease-free survival (DFS) of patients with HCC."}, {"asset": "source:pmid:32216563", "locator": "sections[5] \"Survival Analysis\" paragraph 2", "quote": "Additionally, the Kaplan-Meier plotter online service (http://kmplot.com/analysis/)19 was used for validation of candidates with auto select best cutoff and OS in patients with HCC."}], "state": "complete"}, {"id": "claim-data-access", "statement": "GSE59045 and GSE45436 profiles were obtained from Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/) database. 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Patients with NAFLD/NASH in GSE59045 were grouped according to liver tissue histology: 6 patients in group I (<5% steatosis), 4 in group II (NAFLD, 30% to 50% steatosis), and 5 in group III (NASH)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:32216563"], "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:GSE45436"], "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:GSE45436"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32216563", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1177/1073274820914663", "sha256": "sha256:c6ab418128a4f620a538c59db7d899e2eccacfead5c78674e1a2e1cb0df1bfaf", "bytes": 18039, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1177/1073274820914663", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7137641", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE45436", "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=GSE45436", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE45436", "version": null, "note": "GSE59045 and GSE45436 profiles were obtained from Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/) database. 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Additionally, the Kaplan-Meier plotter online service (http://kmplot.com/analysis/)19 was used for validation of candidates with auto select best cutoff and OS in patients with HCC."}}, {"id": "method-2", "family": "group_comparison", "specific": "mann_whitney", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_mann_whitney"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Mann-Whitney"}}, {"id": "method-3", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "log-rank"}}, {"id": "method-4", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "χ2"}}], "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": ["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. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE59045", "GSE45436", "GSE60502", "GSE84402"], "resolved_accessions": ["GSE59045", "GSE45436", "GSE60502", "GSE84402"], "statements": ["GSE59045 and GSE45436 profiles were obtained from Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/) database. Patients with NAFLD/NASH in GSE59045 were grouped according to liver tissue histology: 6 patients in group I (<5% steatosis), 4 in group II (NAFLD, 30% to 50% steatosis), and 5 in group III (NASH)."], "basis": "The paper names GSE59045, GSE45436, GSE60502, GSE84402 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": ["survival_km"], "assets": ["source:pmid:32216563", "data:geo:GSE45436", "asset:table:pmid:32216563:1", "asset:table:pmid:32216563:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE45436"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:19:11Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 14628, "completion_tokens": 2436, "cached_tokens": 4864}}, "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:32216563", "type": "paper", "label": "pmid:32216563"}, {"id": "source:pmid:32216563", "type": "manuscript", "label": "PMID 32216563 full text"}, {"id": "data:geo:GSE45436", "type": "dataset", "label": "GEO GSE45436"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:32216563", "type": "paper", "label": "pmid:32216563"}, {"id": "source:pmid:32216563", "type": "manuscript", "label": "PMID 32216563 full text"}, {"id": "data:geo:GSE45436", "type": "dataset", "label": "GEO GSE45436"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-32216563", "type": "extraction", "used": ["source:pmid:32216563"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE45436", "type": "accession_resolution", "used": ["data:geo:GSE45436"], "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:32216563", "parent_hash": "sha256:b630c72a6a4c3e39ab4e5ce021e444be3649ddff8bd1d74b0f8b34cb102e6a7f", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE45436 licence not read", "asset:data:geo:GSE45436 not downloaded", "asset:data:geo:GSE59045 licence not read", "asset:data:geo:GSE59045 not downloaded", "asset:data:geo:GSE60502 licence not read", "asset:data:geo:GSE60502 not downloaded", "asset:data:geo:GSE84402 licence not read", "asset:data:geo:GSE84402 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Liver Hepatocellular Carcinoma (The Cancer Genome Atlas [TCGA], Provisional) database in cBioPortal for cancer genomics web service was used for identifying potential candidate biomarkers for predicting the overall survival (OS) and disease-free survival (DFS) of patients with HCC. Additionally, the Kaplan-Meier plotter online service (http://kmplot.com/analysis/)19 was used for validation of candidates with auto select best cutoff and OS in patients with HCC."], "order_basis": "analysis_only", "id": "assay:1"}]}