STC1-Based Activation of NF-κB Signaling Pathway Induces Epthithelial-Mesenchymal Transition Thus Promotes Progression and Temozolomide Resistance of Glioblastoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41020346", "kind": "science-record", "revision": 3, "content_hash": "sha256:6ec8a9d3d8f17f5466b70f11c43f34d08ff113490250c94a09c6827d0603d75e", "created_at": "2026-11-01T20:31:05Z", "updated_at": "2026-11-01T22:14:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "STC1-Based Activation of NF-κB Signaling Pathway Induces Epthithelial-Mesenchymal Transition Thus Promotes Progression and Temozolomide Resistance of Glioblastoma.", "doi": "10.1096/fj.202500095R", "pmid": "41020346", "authors": ["Jia Wang", "Beichen Zhang", "Haoyu Zhou", "Bin Liu", "Xiaobin Bai", "Wei Wu", "Ruichun Li", "Wanfu Xie"], "journal": "FASEB journal : official publication of the Federation of American Societies for Experimental Biology", "year": 2025, "abstract": "Acquired resistance to chemotherapy, especially to temozolomide (TMZ), is a major challenge correlated with the treatment failure of glioblastoma (GBM). Stanniocalcin-1 (STC1) is a glycoprotein hormone involved in multiple biological processes in cancer cells. However, the function and underlying mechanism of STC1 in GBM still remain unclear. To this end, exploring the potential functional role and mechanism of STC1 inducing TMZ resistance becomes an urgent need for individual individualized strategies for GBM. The GSE151680 dataset was obtained from the GEO database; thus, bioinformatic analysis was performed by using R software (version 4.2.0) to screen the differentially expressed genes correlated to TMZ resistance in GBM. Cox regression and nonnegative matrix factorization (NMF) analysis were conducted to establish a prognostic model. Additionally, immunohistochemistry (IHC) staining, qRT-PCR, and western blot were used to investigate the expression of STC1 in GBM tissues and non-tumor controls. Mechanically, loss-of-function and gain-of-function assays were performed to validate the biological functions of STC1 on the malignant biological characters and TMZ resistance of GBM cells. Besides, the enrichment analysis was performed to investigate the downstream pathway of STC1. In this study, STC1 was selected as the gene candidate correlated to TMZ resistance according to the results of Cox regression and NMF analysis. Additionally, increased expression of STC1 could be observed in GBM and was significantly correlated to poor prognosis in GBM. Besides, multiple malignant characters including proliferation, migration, invasion, tumorigenesis, and TMZ resistance of GBM could be markedly reduced by exogenous downregulation of STC1; contrarily, overexpression of STC1 promoted the malignant behaviors and drug resistance of GBM cells. Moreover, GO, KEGG, and GSEA analysis revealed that STC1 induced epithelial-mesenchymal transition (EMT) via activation of NF-κB signaling. Furthermore, the treatment of TNF-α (an activator of the NF-κB pathway) partially reversed the inhibitory effect of sh-STC1 on the proliferation and metastasis in GBM cells. In conclusion, STC1 induced EMT thus enhances the malignancies and drug resistance of GBM cells by activating the NF-κB pathway, providing new evidence for clinical drug development in GBM.", "claims": [{"id": "claim-method", "statement": "The prognostic model was conducted through Cox regression analysis using the survival R package, in which the top 20 prognosis‐related risk genes were presented and further evaluated by the Brier score value and the SHapley Additive exPlanations value (SHAP).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41020346", "locator": "sections[5] \"Construction of the Prognostic Model and Predictive Performance Evaluation\" paragraph 2", "quote": "The prognostic model was conducted through Cox regression analysis using the survival R package, in which the top 20 prognosis‐related risk genes were presented and further evaluated by the Brier score value and the SHapley Additive exPlanations value (SHAP)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used to support the findings of this study are available from the corresponding author upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41020346", "locator": "sections[33] \"Data Availability Statement\" paragraph 2", "quote": "The data used to support the findings of this study are available from the corresponding author upon request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In conclusion, STC1 induced EMT thus enhances the malignancies and drug resistance of GBM cells by activating the NF‐κB pathway, providing new evidence for clinical drug development in GBM.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41020346", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In conclusion, STC1 induced EMT thus enhances the malignancies and drug resistance of GBM cells by activating the NF‐κB pathway, providing new evidence for clinical drug development in GBM."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In conclusion, STC1 induced EMT thus enhances the malignancies and drug resistance of GBM cells by activating the NF‐κB pathway, providing new evidence for clinical drug development in GBM.", "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:41020346"], "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:GSE151680"], "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:GSE151680"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41020346", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1096/fj.202500095R", "sha256": "sha256:f0f7e2be5de022671febac39fa632bb9bce157468849b65da59a1a5774a7648d", "bytes": 48579, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1096/fj.202500095R", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12477750", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE151680", "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=GSE151680", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE151680", "version": null, "note": "The data used to support the findings of this study are available from the corresponding author upon request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data used to support the findings of this study are available from the corresponding author upon request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4588126", "GSM4588127", "GSM4588128", "GSM4588129", "GSM4588130", "GSM4588131", "GSM4588132", "GSM4588133", "GSM4588134", "GSM4588135", "GSM4588136", "GSM4588137"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "16791", "taxon": "Homo sapiens", "title": "Ferroptosis-related Gene Signature Predicts Glioma Cell Death and Glioma Patient Progression", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE151680 not downloaded", "asset:data:geo:GSE151680 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 prognostic model was conducted through Cox regression analysis using the survival R package, in which the top 20 prognosis‐related risk genes were presented and further evaluated by the Brier score value and the SHapley Additive exPlanations value (SHAP)."}}, {"id": "method-2", "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": ["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": ["GSE151680"], "resolved_accessions": ["GSE151680"], "statements": ["The data used to support the findings of this study are available from the corresponding author upon request."], "basis": "The paper names GSE151680 in GEO database 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:41020346", "data:geo:GSE151680"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE151680"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T20:02:08Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14744, "completion_tokens": 1452, "cached_tokens": 256}}, "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:41020346", "type": "paper", "label": "pmid:41020346"}, {"id": "source:pmid:41020346", "type": "manuscript", "label": "PMID 41020346 full text"}, {"id": "data:geo:GSE151680", "type": "dataset", "label": "GEO GSE151680"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:41020346", "type": "paper", "label": "pmid:41020346"}, {"id": "source:pmid:41020346", "type": "manuscript", "label": "PMID 41020346 full text"}, {"id": "data:geo:GSE151680", "type": "dataset", "label": "GEO GSE151680"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-41020346", "type": "extraction", "used": ["source:pmid:41020346"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE151680", "type": "accession_resolution", "used": ["data:geo:GSE151680"], "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:41020346", "parent_hash": "sha256:0f77ee7785f3c90cfa8b1cbaa0fd9f175ea5bf3755fdb9840e9fd4ea4d874833", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE151680 licence not read", "asset:data:geo:GSE151680 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": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["establish a prognostic model. Additionally, immunohistochemistry (IHC) staining, qRT-PCR, and western blot we", "c model. Additionally, immunohistochemistry (IHC) staining, qRT-PCR, and western blot were us"], "order_basis": "paper_text_order:985", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ohistochemistry (IHC) staining, qRT-PCR, and western blot were used to investigate the expression of S"], "order_basis": "paper_text_order:1034", "id": "assay:2"}, {"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": ["can Type Culture Collection (ATCC, USA) were cultured in Dulbecco's Modified Eagle's media (DMEM, Gib"], "order_basis": "paper_text_order:3159", "id": "assay:3"}, {"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 prognostic model was conducted through Cox regression analysis using the survival R package, in which the top 20 prognosis‐related risk genes were presented and further evaluated by the Brier score value and the SHapley Additive exPlanations value (SHAP)."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}