FGF-trapping hampers cancer stem-like cells in uveal melanoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37165394", "kind": "science-record", "revision": 3, "content_hash": "sha256:a8ff339851f36cc3a6c04c89828e783d561768d2abecda2d4badbc00b0c903ac", "created_at": "2026-11-01T19:01:50Z", "updated_at": "2026-11-01T22:09:25Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "FGF-trapping hampers cancer stem-like cells in uveal melanoma.", "doi": "10.1186/s12935-023-02903-z", "pmid": "37165394", "authors": ["Alessandra Loda", "Stefano Calza", "Arianna Giacomini", "Cosetta Ravelli", "Adwaid Manu Krishna Chandran", "Chiara Tobia", "Giovanna Tabellini", "Silvia Parolini", "Francesco Semeraro", "Roberto Ronca", "Sara Rezzola"], "journal": "Cancer cell international", "year": 2023, "abstract": "BACKGROUND: Cancer stem-like cells (CSCs) are a subpopulation of tumor cells responsible for tumor initiation, metastasis, chemoresistance, and relapse. Recently, CSCs have been identified in Uveal Melanoma (UM), which represents the most common primary tumor of the eye. UM is highly resistant to systemic chemotherapy and effective therapies aimed at improving overall survival of patients are eagerly required.\nMETHODS: Herein, taking advantage from a pan Fibroblast Growth Factor (FGF)-trap molecule, we singled out and analyzed a UM-CSC subset with marked stem-like properties. A hierarchical clustering of gene expression data publicly available on The Cancer Genome Atlas (TCGA) was performed to identify patients' clusters.\nRESULTS: By disrupting the FGF/FGF receptor (FGFR)-mediated signaling, we unmasked an FGF-sensitive UM population characterized by increased expression of numerous stemness-related transcription factors, enhanced aldehyde dehydrogenase (ALDH) activity, and tumor-sphere formation capacity. Moreover, FGF inhibition deeply affected UM-CSC survival in vivo in a chorioallantoic membrane (CAM) tumor graft assay, resulting in the reduction of tumor growth. At clinical level, hierarchical clustering of TCGA gene expression data revealed a strong correlation between FGFs/FGFRs and stemness-related genes, allowing the identification of three distinct clusters characterized by different clinical outcomes.\nCONCLUSIONS: Our findings support the evidence that the FGF/FGFR axis represents a master regulator of cancer stemness in primary UM tumors and point to anti-FGF treatments as a novel therapeutic strategy to hit the CSC component in UM.", "claims": [{"id": "claim-method", "statement": "Data were clustered using hierarchical clustering with Euclidean distance metric and Ward’s agglomerative clustering method [48].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37165394", "locator": "sections[13] \"Statistical analyses\" paragraph 3", "quote": "Data were clustered using hierarchical clustering with Euclidean distance metric and Ward’s agglomerative clustering method [48]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data are included in the study and available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37165394", "locator": "sections[25] \"Availability of data and materials\" paragraph 2", "quote": "All data are included in the study and available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "FGF/FGFR blockade targets the UM cancer stem-like subpopulation and inhibits UM growth in vitro and in vivo, while FGF/FGFR expression is linked to stemness and poorer prognosis in UM patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37165394", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "By disrupting the FGF/FGF receptor (FGFR)-mediated signaling, we unmasked an FGF-sensitive UM population characterized by increased expression of numerous stemness-related transcription factors, enhanced aldehyde dehydrogenase (ALDH) activity, and tumor-sphere formation capacity."}, {"asset": "source:pmid:37165394", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "FGF inhibition deeply affected UM-CSC survival in vivo in a chorioallantoic membrane (CAM) tumor graft assay, resulting in the reduction of tumor growth."}, {"asset": "source:pmid:37165394", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Moreover, FGF inhibition deeply affected UM-CSC survival in vivo in a chorioallantoic membrane (CAM) tumor graft assay, resulting in the reduction of tumor growth."}, {"asset": "source:pmid:37165394", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "At clinical level, hierarchical clustering of TCGA gene expression data revealed a strong correlation between FGFs/FGFRs and stemness-related genes, allowing the identification of three distinct clusters characterized by different clinical outcomes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "FGF/FGFR blockade targets the UM cancer stem-like subpopulation and inhibits UM growth in vitro and in vivo, while FGF/FGFR expression is linked to stemness and poorer prognosis in UM patients.", "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:37165394"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37165394", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12935-023-02903-z", "sha256": "sha256:f401d2834ca5df5cd357f21e5eca70ec2b189681a0184646b1d5b63bb53d116f", "bytes": 56496, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12935-023-02903-z", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10173517", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "clustering", "specific": "hierarchical", "label": "Clustering", "dsl_operations": ["hierarchical_cluster"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["feature_matrix"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Data were clustered using hierarchical clustering with Euclidean distance metric and Ward’s agglomerative clustering method [48]."}}, {"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"}}, {"id": "method-3", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {"p_value": "Log-rank test p-value"}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Log-rank"}}, {"id": "method-4", "family": "image_quantification", "specific": "densitometry", "label": "Image analysis / quantification", "dsl_operations": ["segment_objects", "quantify_intensity"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["image_stack"], "evidence": {"score": 0.8, "band": "high", "quote": "Densitometr"}}], "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["hierarchical_cluster"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: hierarchical."}, "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": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": ["All data are included in the study and available from the corresponding author on reasonable request."], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": ["hierarchical_cluster"], "assets": ["source:pmid:37165394"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:39:11Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 16753, "completion_tokens": 1566, "cached_tokens": 128}}, "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:37165394", "type": "paper", "label": "pmid:37165394"}, {"id": "source:pmid:37165394", "type": "manuscript", "label": "PMID 37165394 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37165394", "type": "paper", "label": "pmid:37165394"}, {"id": "source:pmid:37165394", "type": "manuscript", "label": "PMID 37165394 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37165394", "type": "extraction", "used": ["source:pmid:37165394"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "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:37165394", "parent_hash": "sha256:f9183e5babc9bc975fb42095919d1cf09c5389733953f5aedc9fd2d911d5db85", "fork_of": null, "generation": 2}, "gaps": ["execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["F inhibition deeply affected UM-CSC survival in vivo in a chorioallantoic membrane (CAM) tumor gr"], "order_basis": "paper_text_order:1097", "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": ["ger (Leiden University, The Netherlands) and cultured in RPMI 1640 medium supplemented with 100 U/mL"], "order_basis": "paper_text_order:1827", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["n phosphorylation. Densitometric analysis of immunoreactive band shown in Fig. 1D normalized to GAPDH pr"], "order_basis": "paper_text_order:6151", "id": "assay:3"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["e independent experiments. C) Representative flow cytometry dot plots of Aldefluor + cells. The gate ref", "4. Analysis of ALDH activity. Representative flow cytometry dot plots of Aldefluor+ cells of control or"], "order_basis": "paper_text_order:6778", "id": "assay:4"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["Table SII. Oligonucleotide primers used for qPCR analysis."], "order_basis": "paper_text_order:8005", "id": "assay:5"}, {"role": "analysis", "definition_id": "clustering", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["hierarchical_cluster"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Data were clustered using hierarchical clustering with Euclidean distance metric and Ward’s agglomerative clustering method [48]."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}