Identification and validation of stromal-tumor microenvironment-based subtypes tightly associated with PD-1/PD-L1 immunotherapy and outcomes in patients with gastric cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32226313", "kind": "science-record", "revision": 8, "content_hash": "sha256:a97cdcff9283125f9987178824abfd9b1e40a17484340a343403dad173601575", "created_at": "2026-11-01T15:40:58Z", "updated_at": "2026-11-01T22:44:42Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of stromal-tumor microenvironment-based subtypes tightly associated with PD-1/PD-L1 immunotherapy and outcomes in patients with gastric cancer.", "doi": "10.1186/s12935-020-01173-3", "pmid": "32226313", "authors": ["Qianqian Ren", "Peng Zhu", "Hui Zhang", "Tianhe Ye", "Dehan Liu", "Zhao Gong", "Xiangwen Xia"], "journal": "Cancer cell international", "year": 2020, "abstract": "BACKGROUND: Immunotherapies targeting programmed cell death 1 (PD-1) and programmed death-ligand 1 (PD-L1) have been approved for gastric cancer (GC) patients. However, a large proportion of patients with T-cell-inflamed tumor microenvironment do not respond to the PD-1/PD-L1 blockade. The stromal component of the tumor microenvironment has been associated with immunotherapy. This study aims to explore the clinical significance of the non-immune cells in the tumor microenvironment and their potential as biomarkers for immunotherapy.\nMETHODS: A total of 383 patients with GC from the Cancer Genome Atlas (TCGA) cohort, 300 patients with GC from the GSE62254 cohort in Gene Expression Omnibus (GEO) were included in the study. A stromal score was generated using the ESTIMATE algorithm, and the likelihood of response to PD-1/PD-L1 immunotherapy of GC patients was predicted using the TIDE algorithm. The prognostic value of the stromal score from GC cases was evaluated by the Kaplan-Meier method and Cox regression analysis. Gene set enrichment analysis (GSEA) was also conducted.\nRESULTS: The stromal score showed significant differences in different molecular subtypes and T stages. Multivariate analyses further confirmed that the stromal score was an independent indicator of overall survival (OS) in the two cohorts. The low stromal score group showed higher tumor mutation burden (TMB) and micro-satellite instability (MSI), and was more sensitive to immune checkpoint inhibitor according to the TIDE algorithm. Activation of the transforming growth factor and epithelial-mesenchymal transition were observed in the high stromal score subtype, which is associated with T-cell suppression, and may be responsible for resistance to PD-1/PD-L1 therapy. BPIFB2 was confirmed as a hub gene relevant to immunotherapy.\nCONCLUSION: The stromal score was associated with cancer progression and molecular subtypes, and may serve as a novel biomarker for predicting the prognosis and response to immunotherapy in patients with GC.", "claims": [{"id": "claim-method", "statement": "Deseq2 was used for performing data analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32226313", "locator": "sections[4] \"Identification of deferentially expressed genes (DEGs)\" paragraph 2", "quote": "Deseq2 was used for performing data analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are available from TCGA and GEO databases.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32226313", "locator": "sections[25] \"Availability of data and materials\" paragraph 2", "quote": "The data that support the findings of this study are available from TCGA and GEO databases."}], "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:32226313"], "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:GSE62254"], "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:GSE62254"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32226313", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12935-020-01173-3", "sha256": "sha256:538f87be68393e10e57366c78b0d9c00319cc7cd2eefa2ead6796a26d2b338f7", "bytes": 40813, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12935-020-01173-3", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7092673", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE62254", "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=GSE62254", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE62254", "version": null, "note": "The data that support the findings of this study are available from TCGA and GEO databases.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data that support the findings of this study are available from TCGA and GEO databases.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1523727", "GSM1523728", "GSM1523729", "GSM1523744", "GSM1523745", "GSM1523746", "GSM1523747", "GSM1523748", "GSM1523765", "GSM1523768", "GSM1523769", "GSM1523770", "GSM1523771", "GSM1523772", "GSM1523773", "GSM1523774", "GSM1523775", "GSM1523776", "GSM1523777", "GSM1523778", "GSM1523779", "GSM1523780", "GSM1523781", "GSM1523782", "GSM1523783", "GSM1523784", "GSM1523785", "GSM1523786", "GSM1523787", "GSM1523788", "GSM1523789", "GSM1523790", "GSM1523791", "GSM1523792", "GSM1523793", "GSM1523794", "GSM1523795", "GSM1523796", "GSM1523797", "GSM1523798", "GSM1523799", "GSM1523800", "GSM1523801", "GSM1523802", "GSM1523803", "GSM1523804", "GSM1523805", "GSM1523806", "GSM1523807", "GSM1523808", "GSM1523809", "GSM1523810", "GSM1523811", "GSM1523812", "GSM1523813", "GSM1523814", "GSM1523815", "GSM1523816", "GSM1523817", "GSM1523818", "GSM1523819", "GSM1523820", "GSM1523821", "GSM1523822", "GSM1523823", "GSM1523824", "GSM1523825", "GSM1523826", "GSM1523827", "GSM1523828", "GSM1523829", "GSM1523830", "GSM1523831", "GSM1523832", "GSM1523833", "GSM1523834", "GSM1523835", "GSM1523836", "GSM1523837", "GSM1523838", "GSM1523839", "GSM1523840", "GSM1523841", "GSM1523842", "GSM1523843", "GSM1523844", "GSM1523845", "GSM1523846", "GSM1523847", "GSM1523848", "GSM1523849", "GSM1523850", "GSM1523851", "GSM1523852", "GSM1523853", "GSM1523854", "GSM1523855", "GSM1523856", "GSM1523857", "GSM1523858", "GSM1523859", "GSM1523860", "GSM1523861", "GSM1523862", "GSM1523863", "GSM1523864", "GSM1523865", "GSM1523866", "GSM1523867", "GSM1523868", "GSM1523869", "GSM1523870", "GSM1523871", "GSM1523872", "GSM1523873", "GSM1523874", "GSM1523875", "GSM1523876", "GSM1523877", "GSM1523878", "GSM1523879", "GSM1523880", "GSM1523881", "GSM1523882", "GSM1523883", "GSM1523884", "GSM1523885", "GSM1523886", "GSM1523887", "GSM1523888", "GSM1523889", "GSM1523890", "GSM1523891", "GSM1523892", "GSM1523893", "GSM1523894", "GSM1523895", "GSM1523896", "GSM1523897", "GSM1523898", "GSM1523899", "GSM1523901", "GSM1523903", "GSM1523904", "GSM1523905", "GSM1523906", "GSM1523908", "GSM1523909", "GSM1523910", "GSM1523911", "GSM1523918", "GSM1523919", "GSM1523920", "GSM1523921", "GSM1523922", "GSM1523923", "GSM1523924", "GSM1523925", "GSM1523926", "GSM1523927", "GSM1523928", "GSM1523929", "GSM1523930", "GSM1523931", "GSM1523932", "GSM1523933", "GSM1523934", "GSM1523935", "GSM1523936", "GSM1523937", "GSM1523938", "GSM1523939", "GSM1523940", "GSM1523941", "GSM1523942", "GSM1523943", "GSM1523944", "GSM1523945", "GSM1523946", "GSM1523947", "GSM1523948", "GSM1523949", "GSM1523950", "GSM1523951", "GSM1523952", "GSM1523953", "GSM1523954", "GSM1523955", "GSM1523956", "GSM1523957", "GSM1523958", "GSM1523959", "GSM1523960", "GSM1523961", "GSM1523962", "GSM1523963", "GSM1523964", "GSM1523965", "GSM1523966", "GSM1523967", "GSM1523968", "GSM1523969", "GSM1523970", "GSM1523971", "GSM1523972", "GSM1523973", "GSM1523974", "GSM1523975", "GSM1523976", "GSM1523977", "GSM1523978", "GSM1523979", "GSM1523980", "GSM1523981", "GSM1523982", "GSM1523983", "GSM1523984", "GSM1523985", "GSM1523986", "GSM1523987", "GSM1523988", "GSM1523989", "GSM1523990", "GSM1523991", "GSM1523992", "GSM1523993", "GSM1523994", "GSM1523995", "GSM1523996", "GSM1523997", "GSM1523998", "GSM1523999", "GSM1524000", "GSM1524001", "GSM1524002", "GSM1524003", "GSM1524004", "GSM1524005", "GSM1524006", "GSM1524007", "GSM1524008", "GSM1524009", "GSM1524010", "GSM1524011", "GSM1524012", "GSM1524013", "GSM1524014", "GSM1524015", "GSM1524016", "GSM1524017", "GSM1524018", "GSM1524019", "GSM1524020", "GSM1524021", "GSM1524022", "GSM1524023", "GSM1524024", "GSM1524025", "GSM1524026", "GSM1524027", "GSM1524028", "GSM1524029", "GSM1524030", "GSM1524031", "GSM1524032", "GSM1524033", "GSM1524034", "GSM1524035", "GSM1524036", "GSM1524037", "GSM1524038", "GSM1524039", "GSM1524040", "GSM1524041", "GSM1524042", "GSM1524043", "GSM1524044", "GSM1524045", "GSM1524046", "GSM1524047", "GSM1524048", "GSM1524049", "GSM1524050", "GSM1524051", "GSM1524052", "GSM1524053", "GSM1524054", "GSM1524055", "GSM1524056", "GSM1524057", "GSM1524058", "GSM1524059", "GSM1524060", "GSM1524061", "GSM1524062", "GSM1524068", "GSM1524069", "GSM1524070", "GSM1524071", "GSM1524072"], "sample_count": 300, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Molecular analysis of gastric cancer identifies discrete subtypes associated with distinct clinical characteristics and survival outcomes: the ACRG (Asian Cancer Research Group) study [gastric tumors]", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:32226313:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:fd94ee348e2f454fd9036383a349668ae753c860c9ab523efa772d11d941074c", "bytes": 1432, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[1]#Tab1", "version": null, "note": "Stromal score expression and clinicopathological factors in TCGA cases", "structure": {"pmcid": "PMC7092673", "section_index": 9, "section_title": "Clinicopathological characteristics of stromal subtypes", "row_count": 35, "column_count": 4}, "table": {"label": "Table 1", "caption": "Stromal score expression and clinicopathological factors in TCGA cases", "rows": [["Characteristics", "Stromal score", "p-value"], ["Low (n = 192) (%)", "High (n = 191) (%)", ""], ["Age (year)", "", "", "0.6894"], ["≤ 65", "79 (41.1)", "83 (43.5)", ""], ["> 65", "112 (58.3)", "106 (55.5)", ""], ["Unknown", "1 (0.5)", "2 (1)", ""], ["Gender", "", "", "0.4945"], ["Male", "130 (67.7)", "122 (63.9)", ""], ["Female", "62 (32.3)", "69 (36.1)", ""], ["T_stage", "", "", "0.0002869"], ["T1", "18 (9.4)", "2 (1)", ""], ["T2", "47 (24.5)", "34 (17.8)", ""], ["T3", "80 (41.7)", "88 (46.1)", ""], ["T4", "45 (23.4)", "61 (31.9)", ""], ["Unknown", "2 (1)", "6 (3.1)", ""], ["N_stage", "", "", "0.5958"], ["N0", "60 (31.3)", "51 (26.7)", ""], ["N1", "55 (28.6)", "51 (26.7)", ""], ["N2", "38 (19.8)", "36 (18.8)", ""], ["N3", "32 (16.7)", "42 (21.9)", ""], ["Unknown", "7 (3.6)", "11 (5.9)", ""], ["M_stage", "", "", "1"], ["M0", "170 (88.5)", "169 (88.5)", ""], ["M1", "13 (6.8)", "12 (6.3)", ""], ["Unknown", "9 (4.7)", "10 (5.2)", ""], ["Pathologic stage", "", "", "0.3686"], ["I + II", "89 (46.4)", "77 (40.3)", ""], ["III + IV", "97 (50.5)", "104 (54.5)", ""], ["Unknown", "6 (3.1)", "10 (5.2)", ""], ["Molecular_subtype", "", "", "1.36E−06"], ["CIN", "128 (66.7)", "95 (49.7)", ""], ["EBV", "13 (6.8)", "17 (8.9)", ""], ["GS", "8 (4.2)", "42 (22.0)", ""], ["HM-SNV", "5 (2.6)", "2 (1)", ""], ["MSI", "38 (19.8)", "35 (18.3)", ""]], "row_count": 35, "column_count": 4, "numeric_cells": 63, "header_rows": 2, "locator": "section[9]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:32226313:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0ef71ea64c95857505ca469f04a5703ef5cb4bccec843c97036b104ffdfa646c", "bytes": 838, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#Tab2", "version": null, "note": "Univariate and multivariate analyses of stromal score and clinicopathological factors for OS in TCGA cases", "structure": {"pmcid": "PMC7092673", "section_index": 10, "section_title": "The stromal score is involved in outcomes of GC subtypes and is associated with tumor progression", "row_count": 9, "column_count": 7}, "table": {"label": "Table 2", "caption": "Univariate and multivariate analyses of stromal score and clinicopathological factors for OS in TCGA cases", "rows": [["Factor", "Univariate analysis", "Multivariate analysis"], ["HR", "p value", "CI95", "HR", "p value", "CI95"], ["Age", "0.67", "0.021", "0.48–0.94", "0.53", "0.001", "0.37–0.77"], ["Gender", "1.26", "0.204", "0.88–1.82", "1.35", "0.133", "0.91–1.99"], ["T_stage", "0.48", "0.001", "0.31–0.75", "0.7", "0.182", "0.42–1.18"], ["M_stage", "0.4", "0.001", "0.23–0.7", "0.39", "0.003", "0.21–0.72"], ["N_stage", "0.45", "0", "0.29–0.7", "0.6", "0.115", "0.32–1.13"], ["TNM stage", "0.43", "0", "0.3–0.63", "0.76", "0.359", "0.43–1.36"], ["Stromal_group", "0.66", "0.015", "0.47–0.92", "0.62", "0.008", "0.43–0.88"]], "row_count": 9, "column_count": 7, "numeric_cells": 44, "header_rows": 2, "locator": "section[10]/table-wrap[1]#Tab2"}}], "gaps": ["asset:data:geo:GSE62254 not downloaded", "asset:data:geo:GSE62254 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "deseq2", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Deseq2 was used for performing data analysis."}}, {"id": "method-2", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "Kaplan-Meier"}}, {"id": "method-3", "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": 0.7, "band": "medium", "quote": "Cox regression"}}, {"id": "method-4", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log-rank"}}], "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: deseq2."}, "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": ["GSE62254"], "resolved_accessions": ["GSE62254"], "statements": ["The data that support the findings of this study are available from TCGA and GEO databases."], "basis": "The paper names GSE62254 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:32226313", "data:geo:GSE62254", "asset:table:pmid:32226313:1", "asset:table:pmid:32226313:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE62254"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:19:05Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 34471, "completion_tokens": 1433, "cached_tokens": 11520}}, "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:32226313", "type": "paper", "label": "pmid:32226313"}, {"id": "source:pmid:32226313", "type": "manuscript", "label": "PMID 32226313 full text"}, {"id": "data:geo:GSE62254", "type": "dataset", "label": "GEO GSE62254"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:32226313", "type": "paper", "label": "pmid:32226313"}, {"id": "source:pmid:32226313", "type": "manuscript", "label": "PMID 32226313 full text"}, {"id": "data:geo:GSE62254", "type": "dataset", "label": "GEO GSE62254"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-32226313", "type": "extraction", "used": ["source:pmid:32226313"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE62254", "type": "accession_resolution", "used": ["data:geo:GSE62254"], "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:32226313", "parent_hash": "sha256:2729ff717f45429f079afb725c0b1e415544a00dc0d67a4527d502d7702eb149", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE62254 licence not read", "asset:data:geo:GSE62254 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Deseq2 was used for performing data analysis."], "order_basis": "analysis_only", "id": "assay:1"}]}