Inhibition of stress proteins TRIB3 and STC2 potentiates sorafenib sensitivity in hepatocellular carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37389061", "kind": "science-record", "revision": 4, "content_hash": "sha256:206df0c541244f3388436ae3751f2792700927152ccb2d1e2fe898422a15abb9", "created_at": "2026-11-01T19:02:09Z", "updated_at": "2026-11-01T22:52:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Inhibition of stress proteins TRIB3 and STC2 potentiates sorafenib sensitivity in hepatocellular carcinoma.", "doi": "10.1016/j.heliyon.2023.e17295", "pmid": "37389061", "authors": ["Sheng Zhou", "Huanji Xu", "Tianhong Wei"], "journal": "Heliyon", "year": 2023, "abstract": "Sorafenib resistance is one of the main obstacles to the treatment of advanced hepatocellular carcinoma (HCC). Stress proteins TRIB3 and STC2 confer cell resistance to a variety of stresses, including hypoxia, nutritional deprivation, and other perturbations, which induce endoplasmic reticulum stress. However, the role of TRIB3 and STC2 in sorafenib sensitivity to HCC remains unclear. In this study, our results indicated that the common differentially expressed genes (DEGs) in sorafenib-treated HCC cells obtained from the NCBI-GEO database (Huh7 and Hep3B cells; GSE96796) included TRIB3, STC2, HOXD1, C2orf82, ADM2, RRM2, and UNC93A. The most significantly upregulated DEGs were TRIB3 and STC2, which were both stress protein genes. Bioinformatic analysis in NCBI public databases indicated that TRIB3 and STC2 were highly expressed in HCC tissues and closely associated with poor prognoses in HCC patients. Further investigation showed that inhibition of TRIB3 or STC2 with siRNA could enhance the anti-cancer effect of sorafenib in HCC cell lines. In conclusion, our study showed that stress proteins TRIB3 and STC2 are closely associated with sorafenib resistance in HCC. The combination of TRIB3 or STC2 inhibition and sorafenib may be a promising therapeutic strategy for HCC.", "claims": [{"id": "claim-method", "statement": "A series of R BIOCONDUCTOR packages was used to analyze the dataset, raw datasets were normalized, and DEGs were screened out with LIMMA via P-value >0.05 and |log2 (fold change)|>1 cut-off.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37389061", "locator": "sections[8] \"Identification of differentially expressed\" paragraph 2", "quote": "A series of R BIOCONDUCTOR packages was used to analyze the dataset, raw datasets were normalized, and DEGs were screened out with LIMMA via P-value >0.05 and |log2 (fold change)|>1 cut-off."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data associated with this study has been deposited at GEO database under the accession number GSE96796.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37389061", "locator": "sections[20] \"Data availability statement\" paragraph 2", "quote": "Data associated with this study has been deposited at GEO database under the accession number GSE96796."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "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:37389061"], "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:GSE96796"], "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:GSE96796"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37389061", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.heliyon.2023.e17295", "sha256": "sha256:df69e88c6a522da0a8c53e6a4b1b203f44c85191c5ee884435e99301ba0a1355", "bytes": 35794, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.heliyon.2023.e17295", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10300369", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE96796", "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=GSE96796", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE96796", "version": null, "note": "Data associated with this study has been deposited at GEO database under the accession number GSE96796.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data associated with this study has been deposited at GEO database under the accession number GSE96796.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2544149", "GSM2544150", "GSM2544151", "GSM2544152", "GSM2544153", "GSM2544154", "GSM2544155", "GSM2544156", "GSM2544157", "GSM2544158", "GSM2544159", "GSM2544160", "GSM2544161", "GSM2544162", "GSM2544163", "GSM2544164", "GSM2544165", "GSM2544166", "GSM2544167", "GSM2544168", "GSM2544169", "GSM2544170", "GSM2544171", "GSM2544172"], "sample_count": 24, "group_sizes": null, "group_sizes_basis": null, "platform": "10904;10558", "taxon": "Homo sapiens", "title": "Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma", "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:GSE96796 not downloaded", "asset:data:geo:GSE96796 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "A series of R BIOCONDUCTOR packages was used to analyze the dataset, raw datasets were normalized, and DEGs were screened out with LIMMA via P-value >0.05 and |log2 (fold change)|>1 cut-off."}}, {"id": "method-2", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Student's t-test"}}, {"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": "ANOVA"}}], "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": ["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": ["GSE96796"], "resolved_accessions": ["GSE96796"], "statements": ["Data associated with this study has been deposited at GEO database under the accession number GSE96796."], "basis": "The paper names GSE96796 in Gene Expression Omnibus 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:37389061", "data:geo:GSE96796"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE96796"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:45:31Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11241, "completion_tokens": 1014, "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:37389061", "type": "paper", "label": "pmid:37389061"}, {"id": "source:pmid:37389061", "type": "manuscript", "label": "PMID 37389061 full text"}, {"id": "data:geo:GSE96796", "type": "dataset", "label": "GEO GSE96796"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37389061", "type": "paper", "label": "pmid:37389061"}, {"id": "source:pmid:37389061", "type": "manuscript", "label": "PMID 37389061 full text"}, {"id": "data:geo:GSE96796", "type": "dataset", "label": "GEO GSE96796"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37389061", "type": "extraction", "used": ["source:pmid:37389061"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE96796", "type": "accession_resolution", "used": ["data:geo:GSE96796"], "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:37389061", "parent_hash": "sha256:3e1ee0c56d6acaa61834311669f30d8bb954c74ad1083d268da03c8893ce290d", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE96796 licence not read", "asset:data:geo:GSE96796 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": 0.77, "evidence": ["showed that inhibition of TRIB3 or STC2 with siRNA could enhance the anti-cancer effect of sora"], "order_basis": "paper_text_order:1045", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["KE Biological Technology Company. Cells were cultured in Dulbecco's Modified Eagle Medium supplemente"], "order_basis": "paper_text_order:1644", "id": "assay:2"}, {"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": ["A series of R BIOCONDUCTOR packages was used to analyze the dataset, raw datasets were normalized, and DEGs were screened out with LIMMA via P-value >0.05 and |log2 (fold change)|>1 cut-off."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}