The clinicopathological significance and predictive value for immunotherapy of programmed death ligand-1 expression in Epstein-Barr virus-associated gastric cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34235004", "kind": "science-record", "revision": 5, "content_hash": "sha256:ec040b8e0f0a3f5f5374c14024658c9f08b9a7d1abd5d1b400285d6822505c76", "created_at": "2026-11-01T15:41:42Z", "updated_at": "2026-11-01T18:56:02Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The clinicopathological significance and predictive value for immunotherapy of programmed death ligand-1 expression in Epstein-Barr virus-associated gastric cancer.", "doi": "10.1080/2162402X.2021.1938381", "pmid": "34235004", "authors": ["Xiao-Li Wei", "Qian-Wen Liu", "Fu-Rong Liu", "Sha-Sha Yuan", "Xiao-Fen Li", "Jia-Ning Li", "An-Li Yang", "Yi-Hong Ling"], "journal": "Oncoimmunology", "year": 2021, "abstract": "The effect of anti-programmed cell death 1 (PD-1) antibody in Epstein-Barr virus-associated gastric cancer (EBVaGC) was debatable, and no predictive biomarkers for efficacy have been reported. Public reports on anti-PD-1 antibody monotherapy-treated EBVaGC with available programmed death ligand-1 (PD-L1) expression status were summarized and analyzed. Relevance with clinicopathologic characteristics of PD-L1 expression by immunohistochemistry was analyzed in 159 patients diagnosed with EBVaGC. Relevance with genomic transcriptome and mutation profile of PD-L1 status in EBVaGC was assessed with three datasets, the cancer genome atlas (TCGA), Gene Expression Omnibus (GEO) GSE51575, and GSE62254. Based on the data from 8 reports, patients with positive PD-L1 expression (n = 30) had significantly superior objective response rate (ORR) than patients with negative PD-L1 expression (n = 9) (63.3% vs. 0%, P = .001) in EBVaGC receiving anti-PD-1 antibody monotherapy. PD-L1 positivity was associated with less aggressive clinicopathological characteristics and was an independent predictor for a longer disease-free survival (hazard ratio [HR] and 95% CI: 0.45 [0.22-0.92], P = .03) and overall survival (HR and 95% CI: 0.17 [0.06-0.43], P < .001). Analysis of public EBVaGC transcriptome and mutation datasets revealed enhanced immune-related signal pathways in PD-L1high EBVaGC and distinct mutation patterns in PD-L1low EBVaGC. PD-L1 positivity indicates a subtype of EBVaGC with 'hot' immune microenvironment, lower aggressiveness, better prognosis, and higher sensitivity to anti-PD-1 immunotherapy.", "claims": [{"id": "claim-data-access", "statement": "Data are available on reasonable request. All data generated that are relevant to the results presented in this article are included in this article. Other data that were not relevant for the results presented here are available from the corresponding author Dr. Ling on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34235004", "locator": "sections[20] \"Data sharing statement\" paragraph 2", "quote": "Data are available on reasonable request. All data generated that are relevant to the results presented in this article are included in this article. Other data that were not relevant for the results presented here are available from the corresponding author Dr. Ling on reasonable request."}], "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:34235004"], "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:GSE51575"], "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:GSE51575"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34235004", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1080/2162402X.2021.1938381", "sha256": "sha256:40174fa7d81cf49da4ad476f7ed3028bcddfbe43fe76b59564e3056f0bbceea1", "bytes": 31003, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1080/2162402X.2021.1938381", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8216206", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE51575", "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=GSE51575", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE51575", "version": null, "note": "Data are available on reasonable request. 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"table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:cd10337b89e9c994e60933b59f48734d03032f458d23d66fc15905505d18476c", "bytes": 1742, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#t0001", "version": null, "note": "The effective rate of PD-1/PD-L1 inhibitors stratified by PD-L1 expression in EBVaGC", "structure": {"pmcid": "PMC8216206", "section_index": 10, "section_title": "Efficacy of PD-1/PD-L1 inhibitors in EBVaGC according to PD-L1 expression", "row_count": 12, "column_count": 15}, "table": {"label": "Table 1.", "caption": "The effective rate of PD-1/PD-L1 inhibitors stratified by PD-L1 expression in EBVaGC", "rows": [["Source", "PD-L1 IHC antibody", "PD-L1 evaluation", "PD-1/PD-L1 inhibitors", "Total number of patients", "ORR (%)", "Total number of patients", "Number of patients (number of responders) according to PD-L1 expression"], ["", "", "", "", "", "", "", "< 1%", "≧1%", "< 10%", "≧10%", "< 50%", "≧50%", "≧1%-10%", "≧10%-50%"], ["Tong et al., 2020", "NA", "TC+IC", "PD-1/PD-L1 inhibitors", "7", "42.8", "7", "1 (0)", "6 (3)", "3 (0)", "4 (3)", "6 (2)", "1 (1)", "2 (0)", "3 (2)"], ["Saori et al., 2019", "SP142/SP263", "CPS", "Nivolumab", "4", "25.0", "4", "0", "4 (1)", "4 (1)", "0", "0", "0", "4 (1)", "0"], ["Seung et al., 2018", "22C3", "CPS", "Pembrolizumab", "6", "100.0", "6", "0", "6 (6)", "2 (2)", "4 (4)", "4 (4)", "2 (2)", "2 (2)", "2 (2)"], ["Anshuman et al., 2018", "SP142", "TC+IC", "Avelumab", "1", "100.0", "1", "0", "1 (1)", "0", "1 (1)", "0", "1 (1)", "0", "0"], ["Jinchul et al., 2020", "22C3", "CPS", "Nivolumab/ Pembrolizumab", "4", "50.0", "4", "1 (0)", "3 (2)", "NA", "NA", "NA", "NA", "NA", "NA"], ["F et al., 2019", "SP142", "TC+IC", "Toripalimab", "4", "25.0", "4", "3 (0)", "1 (1)", "3 (0)", "1 (1)", "4 (1)", "0", "0", "1 (1)"], ["Yohei et al., 2020", "SP142/SP263", "CPS", "PD-1 inhibitors", "6", "33.3", "6", "0", "6 (2)", "4 (1)", "2 (1)", "4 (1)", "NA", "4 (1)", "NA"], ["Minsuk et al., 2020", "22C3", "CPS", "Nivolumab/ Pembrolizumab", "7", "42.9", "7", "4 (0)", "3 (3)", "4 (0)", "NA", "4 (0)", "NA", "NA", "NA"], ["Total", "", "", "", "39", "48.7", "39", "9 (0)", "30 (19)", "20 (4)", "12 (10)", "22 (8)", "4 (4)", "12 (4)", "6 (5)"], ["ORR (%)", "", "", "", "", "", "", "0.0", "63.3", "20.0", "83.3", "36.4", "100.0", "33.3", "83.3"]], "row_count": 12, "column_count": 15, "numeric_cells": 121, "header_rows": 1, "locator": "section[10]/table-wrap[1]#t0001"}}, {"id": "asset:table:pmid:34235004:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:717196c7ef4c2ae52f261f52000e0ce32b779a5d981d2393bc8af7db16697669", "bytes": 2014, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#t0002", "version": null, "note": "The clinicopathological relevance of PD-L1 expression in EBVaGC", "structure": {"pmcid": "PMC8216206", "section_index": 11, "section_title": "Association of PD-L1 expression with clinicopathological characteristics in EBVaGC", "row_count": 47, "column_count": 4}, "table": {"label": "Table 2.", "caption": "The clinicopathological relevance of PD-L1 expression in EBVaGC", "rows": [["Characteristics", "PD-L1 expression*", "", "P value"], ["", "Negative, No. (%)", "Positive, No. (%)", ""], ["Age (years, median 57)", "", "", "0.94"], ["≤ 57", "36 (45.0)", "44 (55.0)", ""], ["> 57", "36 (45.6)", "43 (54.4)", ""], ["Sex", "", "", "0.04"], ["Male", "68 (48.2)", "73 (51.8)", ""], ["Female", "4 (22.2)", "14 (77.8)", ""], ["Primary site", "", "", "0.68"], ["Proximal", "35 (46.7)", "40 (53.3)", ""], ["Distal", "26 (47.3)", "29 (52.7)", ""], ["Stump", "9 (42.9)", "12 (57.1)", ""], ["Other", "2 (25.0)", "6 (75.0)", ""], ["Tumor size (cm, median 4.5)", "", "", "0.05"], ["≤ 4.5", "32 (38.1)", "52 (61.9)", ""], ["> 4.5", "40 (53.3)", "35 (46.7)", ""], ["T category**", "", "", "0.14"], ["T1+ T2", "15 (34.9)", "28 (65.1)", ""], ["T3+ T4", "52 (48.1)", "56 (51.9)", ""], ["N category**", "", "", "0.001"], ["N0+ N1", "16 (27.6)", "42 (72.4)", ""], ["N2+ N3", "50 (54.9)", "41 (45.1)", ""], ["M category", "", "", "0.01"], ["M0", "54 (40.9)", "78 (59.1)", ""], ["M1", "18 (66.7)", "9 (33.0)", ""], ["TNM classification", "", "", "0.004"], ["I+II", "16 (29.6)", "38 (70.4)", ""], ["III+IV", "56 (53.3)", "49 (46.7)", ""], ["Tumor differentiation", "", "", "0.81"], ["Poorly differentiated", "40 (44.4)", "50 (55.6)", ""], ["Moderately differentiated", "32 (46.4)", "37 (53.6)", ""], ["Lauren classification**", "", "", "0.81"], ["Intestinal", "22 (46.8)", "25 (53.2)", ""], ["Diffuse", "11 (50.0)", "11 (50.0)", ""], ["Mixed", "37 (43.0)", "49 (57.0)", ""], ["Lymphoepithelioma-like gastric cancer", "", "", "<0.001"], ["No", "38 (67.8)", "18 (32.1)", ""], ["Yes", "28 (30.8)", "63 (69.2)", ""], ["Nervous invasion**", "", "", "0.01"], ["Negative", "15 (29.4)", "36 (70.6)", ""], ["Positive", "51 (51.5)", "48 (48.5)", ""], ["Venous invasion**", "", "", "0.02"], ["Negative", "25 (34.2)", "48 (65.8)", ""], ["Positive", "41 (53.2)", "36 (46.8)", ""], ["HER2 IHC score", "", "", "0.01"], ["0–1", "54 (40.9)", "78 (59.1)", ""], ["2–3", "18 (69.2)", "8 (30.8)", ""]], "row_count": 47, "column_count": 4, "numeric_cells": 84, "header_rows": 1, "locator": "section[11]/table-wrap[1]#t0002"}}, {"id": "asset:table:pmid:34235004:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b9bb82b032951120170277a55178b1ba6f0d362df3566e810e431ca194aa33a3", "bytes": 1855, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#t0003", "version": null, "note": "Univariate and multivariate Cox proportional hazards analysis for progression-free survival and overall survival in EBVaGC", "structure": {"pmcid": "PMC8216206", "section_index": 12, "section_title": "Prognostic relevance of PD-L1 expression in EBVaGC", "row_count": 16, "column_count": 9}, "table": {"label": "Table 3.", "caption": "Univariate and multivariate Cox proportional hazards analysis for progression-free survival and overall survival in EBVaGC", "rows": [["Characteristics", "PFS", "", "", "", "OS", "", "", ""], ["", "Univariate analysis", "", "Multivariate analysis", "", "Univariate analysis", "", "Multivariate analysis", ""], ["", "HR (95% CI)", "P value", "HR (95% CI)", "P value", "HR (95% CI)", "P value", "HR (95% CI)", "P value"], ["Age (≤ 57/> 57)", "0.64 (0.32–1.30)", "0.22", "", "", "1.16 (0.60–2.23)", "0.66", "", ""], ["Sex (Male/Female)", "0.80 (0.28–2.28)", "0.67", "", "", "0.91 (0.32–2.58)", "0.86", "", ""], ["Tumor size (cm, ≤ 4.5/> 4.5)", "2.70 (1.31–5.54)", "0.01", "", "", "3.88 (1.86–8.09)", "<0.001", "", ""], ["TMN classification (I+ II/III+IV)", "27.8 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