Growth and differentiation factor 15 regulates PD-L1 expression in glioblastoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31114328", "kind": "science-record", "revision": 7, "content_hash": "sha256:e5d1d106ef3666a82032a74052be913c6edd5ee7049deab5a8ecdbc2602fe41d", "created_at": "2026-11-01T15:40:45Z", "updated_at": "2026-11-01T21:22:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Growth and differentiation factor 15 regulates PD-L1 expression in glioblastoma.", "doi": "10.2147/CMAR.S192095", "pmid": "31114328", "authors": ["Haiqin Peng", "Zhanzhan Li", "Jun Fu", "Rongrong Zhou"], "journal": "Cancer management and research", "year": 2019, "abstract": "Background: Gliomablastoma multiforme (GBM) is the most fatal form of all brain cancers in human with no successful treatment available. Programmed death-ligand 1 (PD-L1) is a coinhibitory ligand predominantly expressed by tumor cells. Growth differentiation factors (GDFs) are a subfamily of proteins belonging to the transforming growth factor beta superfamily that have functions predominantly in tissue development and cancer. Purpose: To investigat the expression of GDFs in GBMs, and explored the potential regulatory role of GDFs on PD-L1 expression in GBMs. Methods: GEO2R program were analyzed for the mRNA expression data of GDFs in GSE4290 dataset. Analysis of TCGA GBM datasets were further determined the relationship between GDFs and PD-L1. Western blot Western blot was used to detect the expression of PD-L1 in GBM cell lines. Results: GDFs displayed differential patterns of expression with GDF15 and myostatin (MSTN) highly enriched in GBM tissues. We also identified GDF15 as a novel regulator that induces PD-L1 expression in GBM cells. Consistently, GDF15 expression correlated with PD-L1 in TCGA GBM dataset. Further, GDF15 enhanced PD-L1 expression via Smad2/3 pathway in GBM cell line U87, U251 and SHG44, which was inhibited by Smad2/3 inhibitor SIS3. Knockdown of GDF15 attenuated Smad2/3 signaling and reduced PD-L1 expression in A172 and GIC6 glioma cells. Conclusion: GDF15 might be a novel regulator of PD-L1 expression in GBMs; targeting GDF15/PD-L1 pathway might be a promising therapeutic approach for GBM patients.", "claims": [{"id": "claim-method", "statement": "The mRNA expression levels of GDF15 significantly correlated with those of PD-L1 in the TCGA GBM datasets (n=152, Spearman’s correlation r=0.51, P<0.05, Table 1).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31114328", "locator": "sections[10] \"GDF15 expression was correlated with PD-L1 in GBM cell lines and GBM patients\" paragraph 2", "quote": "The mRNA expression levels of GDF15 significantly correlated with those of PD-L1 in the TCGA GBM datasets (n=152, Spearman’s correlation r=0.51, P<0.05, Table 1)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "mRNA expression data (RNA-Seq) of GBMs (n=152) were downloaded from the data portal of TCGA project (https://gdc-portal.nci.nih.gov/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31114328", "locator": "sections[5] \"The Cancer Genome Atlas (TCGA) data analysis\" paragraph 2", "quote": "mRNA expression data (RNA-Seq) of GBMs (n=152) were downloaded from the data portal of TCGA project (https://gdc-portal.nci.nih.gov/)."}], "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:31114328"], "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:GSE4290"], "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:GSE4290"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31114328", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/CMAR.S192095", "sha256": "sha256:dfc08f1083d77d80f07a7a5673a9d9e43f9f14fdbaf902c9e0d94bb6e483e1b7", "bytes": 29195, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/CMAR.S192095", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6497826", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE4290", "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=GSE4290", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE4290", "version": null, "note": "mRNA expression data (RNA-Seq) of GBMs (n=152) were downloaded from the data portal of TCGA project (https://gdc-portal.nci.nih.gov/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "mRNA expression data (RNA-Seq) of GBMs (n=152) were downloaded from the data portal of TCGA project (https://gdc-portal.nci.nih.gov/).", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM97793", "GSM97794", "GSM97795", "GSM97796", "GSM97797", "GSM97798", "GSM97799", "GSM97800", "GSM97801", "GSM97802", "GSM97803", "GSM97804", "GSM97805", "GSM97806", "GSM97807", "GSM97808", "GSM97809", "GSM97810", "GSM97811", "GSM97812", "GSM97813", "GSM97814", "GSM97815", "GSM97816", "GSM97817", "GSM97818", "GSM97819", "GSM97820", "GSM97821", "GSM97822", "GSM97823", "GSM97824", "GSM97825", "GSM97826", "GSM97827", "GSM97828", "GSM97829", "GSM97830", "GSM97831", "GSM97832", "GSM97833", "GSM97834", "GSM97835", "GSM97836", "GSM97837", "GSM97838", "GSM97839", "GSM97840", "GSM97841", "GSM97842", "GSM97843", "GSM97844", "GSM97845", "GSM97846", "GSM97847", "GSM97848", "GSM97849", "GSM97850", "GSM97851", "GSM97852", "GSM97853", "GSM97854", "GSM97855", "GSM97856", "GSM97857", "GSM97858", "GSM97859", "GSM97860", "GSM97861", "GSM97862", "GSM97863", "GSM97864", "GSM97865", "GSM97866", "GSM97867", "GSM97868", "GSM97869", "GSM97870", "GSM97871", "GSM97872", "GSM97873", "GSM97874", "GSM97875", "GSM97876", "GSM97877", "GSM97878", "GSM97879", "GSM97880", "GSM97881", "GSM97882", "GSM97883", "GSM97884", "GSM97885", "GSM97886", "GSM97887", "GSM97888", "GSM97889", "GSM97890", "GSM97891", "GSM97892", "GSM97893", "GSM97894", "GSM97895", "GSM97896", "GSM97897", "GSM97898", "GSM97899", "GSM97900", "GSM97901", "GSM97902", "GSM97903", "GSM97904", "GSM97905", "GSM97906", "GSM97907", "GSM97908", "GSM97909", "GSM97910", "GSM97911", "GSM97912", "GSM97913", "GSM97914", "GSM97915", "GSM97916", "GSM97917", "GSM97918", "GSM97919", "GSM97920", "GSM97921", "GSM97922", "GSM97923", "GSM97924", "GSM97925", "GSM97926", "GSM97927", "GSM97928", "GSM97929", "GSM97930", "GSM97931", "GSM97932", "GSM97933", "GSM97934", "GSM97935", "GSM97936", "GSM97937", "GSM97938", "GSM97939", "GSM97940", "GSM97941", "GSM97942", "GSM97943", "GSM97944", "GSM97945", "GSM97946", "GSM97947", "GSM97948", "GSM97949", "GSM97950", "GSM97951", "GSM97952", "GSM97953", "GSM97954", "GSM97955", "GSM97956", "GSM97957", "GSM97958", "GSM97959", "GSM97960", "GSM97961", "GSM97962", "GSM97963", "GSM97964", "GSM97965", "GSM97966", "GSM97967", "GSM97968", "GSM97969", "GSM97970", "GSM97971", "GSM97972"], "sample_count": 180, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Expression data of glioma samples from Henry Ford Hospital", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:31114328:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:11ae9b977c42ab0a3f3b916a2926f94aaa768457c0d2864082900eeb94e3f968", "bytes": 582, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#T0001", "version": null, "note": "Correlation between PD-L1 and GDFs in GBM (TCGA RNA-seq dataset, n=152)", "structure": {"pmcid": "PMC6497826", "section_index": 10, "section_title": "GDF15 expression was correlated with PD-L1 in GBM cell lines and GBM patients", "row_count": 12, "column_count": 3}, "table": {"label": "Table 1", "caption": "Correlation between PD-L1 and GDFs in GBM (TCGA RNA-seq dataset, n=152)", "rows": [["Genes", "Cytoband", "Spearman’s correlation"], ["GDF15", "19p13.11", "0.51"], ["GDF1", "19p13.11", "0.00"], ["GDF2", "10q11.22", "−0.06"], ["GDF3", "12p13.31", "0.00"], ["GDF5", "20q11.22", "0.20"], ["GDF6", "8q22.1", "−0.12"], ["GDF7", "2p24.1", "0.07"], ["GDF8/MSTN", "2q32.2", "−0.22"], ["GDF9", "5q31.1", "−0.04"], ["GDF10", "10q11.22", "−0.17"], ["GDF11", "12q13.2", "0.14"]], "row_count": 12, "column_count": 3, "numeric_cells": 25, "header_rows": 1, "locator": "section[10]/table-wrap[1]#T0001"}}], "gaps": ["asset:data:geo:GSE4290 not downloaded", "asset:data:geo:GSE4290 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Spearman correlation"}}, {"id": "method-2", "family": null, "specific": null, "label": "Spearman’s correlation", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The mRNA expression levels of GDF15 significantly correlated with those of PD-L1 in the TCGA GBM datasets (n=152, Spearman’s correlation r=0.51, P<0.05, Table 1)."}}], "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": ["spearman_rho"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: spearman."}, "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": ["GSE4290"], "resolved_accessions": ["GSE4290"], "statements": ["mRNA expression data (RNA-Seq) of GBMs (n=152) were downloaded from the data portal of TCGA project (https://gdc-portal.nci.nih.gov/)."], "basis": "The paper names GSE4290 in NCBI Gene Expression Omnibus (GEO), GSE4290 dataset and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["spearman_rho"], "assets": ["source:pmid:31114328", "data:geo:GSE4290", "asset:table:pmid:31114328:1"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE4290"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:44:52Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 25810, "completion_tokens": 1506, "cached_tokens": 528}}, "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:31114328", "type": "paper", "label": "pmid:31114328"}, {"id": "source:pmid:31114328", "type": "manuscript", "label": "PMID 31114328 full text"}, {"id": "data:geo:GSE4290", "type": "dataset", "label": "GEO GSE4290"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:31114328", "type": "paper", "label": "pmid:31114328"}, {"id": "source:pmid:31114328", "type": "manuscript", "label": "PMID 31114328 full text"}, {"id": "data:geo:GSE4290", "type": "dataset", "label": "GEO GSE4290"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-31114328", "type": "extraction", "used": ["source:pmid:31114328"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE4290", "type": "accession_resolution", "used": ["data:geo:GSE4290"], "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:31114328", "parent_hash": "sha256:8de858adaab3e15edcfa8870c9d1caaee926016787ee20519aef8ed078306781", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE4290 licence not read", "asset:data:geo:GSE4290 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ned the relationship between GDFs and PD-L1. Western blot Western blot was used to detect the expressi", "ionship between GDFs and PD-L1. Western blot Western blot was used to detect the expression of PD-L1 i"], "order_basis": "paper_text_order:791", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["ich was inhibited by Smad2/3 inhibitor SIS3. Knockdown of GDF15 attenuated Smad2/3 signaling and re"], "order_basis": "paper_text_order:1313", "id": "assay:2"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["spearman_rho"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Spearman correlation"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}