PD-L1 overexpression in EBV-positive gastric cancer is caused by unique genomic or epigenomic mechanisms.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33479394", "kind": "science-record", "revision": 9, "content_hash": "sha256:37d5e9225774dd46860a6f417ab1ea722564bf6b4bfc334cf40c35dfff56858c", "created_at": "2026-11-01T15:41:23Z", "updated_at": "2026-11-01T22:46:01Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "PD-L1 overexpression in EBV-positive gastric cancer is caused by unique genomic or epigenomic mechanisms.", "doi": "10.1038/s41598-021-81667-w", "pmid": "33479394", "authors": ["Hiroshi Nakano", "Motonobu Saito", "Shotaro Nakajima", "Katsuharu Saito", "Yuko Nakayama", "Koji Kase", "Leo Yamada", "Yasuyuki Kanke", "Hiroyuki Hanayama", "Hisashi Onozawa", "Hirokazu Okayama", "Shotaro Fujita", "Wataru Sakamoto", "Zenichiro Saze", "Tomoyuki Momma", "Kosaku Mimura", "Shinji Ohki", "Akiteru Goto", "Koji Kono"], "journal": "Scientific reports", "year": 2021, "abstract": "Epstein-Barr virus-positive gastric cancer [EBV (+) GC] is a distinct GC subtype with unique genetic and epigenetic aberrations. Here, we examined resected GC samples and publicly available microarray data and The Cancer Genome Atlas (TCGA) database to identify the mechanism underlying overexpression of PD-L1 in EBV (+) GC. We found that high levels of PD-L1 overexpression in EBV (+) GC were caused by focal amplification of CD274. By contrast, relatively high expression of PD-L1 in tumor tissue and infiltrating immune cells correlated with CD8 lymphocyte infiltration and IFN-γ expression via IRF3 activation. Since we reported previously that PD-L1 expression is associated both with the presence of CD8 T cells in the tumor microenvironment and with IFN-γ expression in GC, we examined a database to see whether IFN-γ-associated overexpression of PD-L1 plays a significant role in EBV (+) GC. Immunohistochemical staining showed that expression of the IRF3 signature in clinical GC samples was higher in EBV (+) than in EBV (-) cases. The data presented herein reveal a unique dual mechanism underlying PD-L1 overexpression in EBV (+) GC: high focal amplification of CD274 or IFN-γ-mediated signaling via activation of IRF3.", "claims": [{"id": "claim-method", "statement": "Mann–Whitney U test were used to determine differences between two variables. Spearman’s correlation was used to evaluate the correlations between levels of expression. Pearson correlation analysis was used to examine the relationships between two parameters. ANOVA test was used for multiple comparisons.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33479394", "locator": "sections[13] \"Statistical analysis\" paragraph 2", "quote": "Mann–Whitney U test were used to determine differences between two variables. Spearman’s correlation was used to evaluate the correlations between levels of expression. Pearson correlation analysis was used to examine the relationships between two parameters. ANOVA test was used for multiple comparisons."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We utilized microarray gene methylation profiles from 54 patients with GC and EBV-infected GC cells, using Akata system of recombinant EBV, deposited as GSE31789 on the basis of Illumina Infinium HumanMethylation27 BeadChip5 and analyzed according to our previous study31.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33479394", "locator": "sections[10] \"Microarray data analysis\" paragraph 2", "quote": "We utilized microarray gene methylation profiles from 54 patients with GC and EBV-infected GC cells, using Akata system of recombinant EBV, deposited as GSE31789 on the basis of Illumina Infinium HumanMethylation27 BeadChip5 and analyzed according to our previous study31."}], "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:33479394"], "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:GSE31787"], "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:GSE31787"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33479394", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-021-81667-w", "sha256": 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