Identification of a risk score model based on tertiary lymphoid structure-related genes for predicting immunotherapy efficacy in non-small cell lung cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38558529", "kind": "science-record", "revision": 4, "content_hash": "sha256:3de8c999ed6948266a251dd8fc3e755c611747e4ebefa6b6f3818eebddfe6957", "created_at": "2026-11-01T19:20:31Z", "updated_at": "2026-11-01T22:11:35Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of a risk score model based on tertiary lymphoid structure-related genes for predicting immunotherapy efficacy in non-small cell lung cancer.", "doi": "10.1111/1759-7714.15299", "pmid": "38558529", "authors": ["Shi-Qi Mei", "Jia-Qi Liu", "Zi-Jian Huang", "Wei-Chi Luo", "Ying-Long Peng", "Zhi-Hong Chen", "Yu Deng", "Chong-Rui Xu", "Qing Zhou"], "journal": "Thoracic cancer", "year": 2024, "abstract": "BACKGROUND: Tertiary lymphoid structures (TLSs) affect the prognosis and efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC), but the underlying mechanisms are not well understood.\nMETHODS: TLSs were identified and categorized online from the Cancer Digital Slide Archive (CDSA). Overall survival (OS) and disease-free survival (DFS) were analyzed. GSE111414 and GSE136961 datasets were downloaded from the GEO database. GSVA, GO and KEGG were used to explore the signaling pathways. Immune cell infiltration was analyzed by xCell, ssGSEA and MCP-counter. The analysis of WGCNA, Lasso and multivariate cox regression were conducted to develop a gene risk score model based on the SU2C-MARK cohort.\nRESULTS: TLS-positive was a protective factor for OS according to multivariate cox regression analysis (p = 0.029). Both the TLS-positive and TLS-mature groups exhibited genes enrichment in immune activation pathways. The TLS-mature group showed more activated dendritic cell infiltration than the TLS-immature group. We screened TLS-related genes using WGCNA. Lasso and multivariate cox regression analysis were used to construct a five-genes (RGS8, RUF4, HLA-DQB2, THEMIS, and TRBV12-5) risk score model, the progression free survival (PFS) and OS of patients in the low-risk group were markedly superior to those in the high-risk group (p < 0.0001; p = 0.0015, respectively). Calibration and ROC curves indicated that the combined model with gene risk score and clinical features could predict the PFS of patients who have received immunotherapy more accurately than a single clinical factor.\nCONCLUSIONS: Our data suggested a pivotal role of TLSs formation in survival outcome and immunotherapy response of NSCLC patients. Tumors with mature TLS formation showed more activated immune microenvironment. In addition, the model constructed by TLS-related genes could predict the response to immunotherapy and is meaningful for clinical decision-making.", "claims": [{"id": "claim-method", "statement": "Results from univariate and multivariate Cox regression for OS showed that TLS‐positive was an independent protective factor (Table S3).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38558529", "locator": "sections[11] \"Prognostic value of TLSs in LUAD\" paragraph 4", "quote": "Results from univariate and multivariate Cox regression for OS showed that TLS‐positive was an independent protective factor (Table S3)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Materials, and further enquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38558529", "locator": "sections[22] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Materials, and further enquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "TLS‐positive was a protective factor for OS according to multivariate cox regression analysis (p = 0.029).", "kind": "quantitative", "target": {"value": 0.029, "unit": "p-value", "tolerance": null, "source": "TLS‐positive was a protective factor for OS according to multivariate cox regression analysis (p = 0.029)."}, "evidence": [{"asset": "source:pmid:38558529", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "TLS‐positive was a protective factor for OS according to multivariate cox regression analysis (p = 0.029)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "TLS‐positive was a protective factor for OS according to multivariate cox regression analysis (p = 0.029).", "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:38558529"], "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:GSE111414"], "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:GSE111414"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38558529", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1111/1759-7714.15299", "sha256": "sha256:42b0ed12cc99ac0e2dfdfd5015ec98cd1035ad3df8bbd86b4c38c06ad8ce4ac9", "bytes": 35409, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1111/1759-7714.15299", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11091782", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE111414", "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=GSE111414", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE111414", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Materials, and further enquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Materials, and further enquiries can be directed to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3030378", "GSM3030379", "GSM3030380", "GSM3030381", "GSM3030382", "GSM3030383", "GSM3030384", "GSM3030385", "GSM3030386", "GSM3030387", "GSM3030388", "GSM3030389", "GSM3030390", "GSM3030391", "GSM3030392", "GSM3030393", "GSM3030394", "GSM3030395", "GSM3030396", "GSM3030397"], "sample_count": 20, "group_sizes": null, "group_sizes_basis": null, "platform": "21290", "taxon": "Homo sapiens", "title": "KIR Polymorphism is Associated with Primary Resistance to PD-1 Blockade in Lung Cancer", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE136961", "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=GSE136961", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE136961", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Materials, and further enquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Materials, and further enquiries can be directed to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4063814", "GSM4063815", "GSM4063816", "GSM4063817", "GSM4063818", "GSM4063819", "GSM4063820", "GSM4063821", "GSM4063822", "GSM4063823", "GSM4063824", "GSM4063825", "GSM4063826", "GSM4063827", "GSM4063828", "GSM4063829", "GSM4063830", "GSM4063831", "GSM4063832", "GSM4063833", "GSM4063834"], "sample_count": 21, "group_sizes": null, "group_sizes_basis": null, "platform": "24014", "taxon": "Homo sapiens", "title": "Immune gene signatures for predicting durable clinical benefit of anti-PD-1 immunotherapy in patients with non-small cell lung cancer", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE111414 not downloaded", "asset:data:geo:GSE111414 licence not read", "asset:data:geo:GSE136961 not downloaded", "asset:data:geo:GSE136961 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "Results from univariate and multivariate Cox regression for OS showed that TLS‐positive was an independent protective factor (Table S3)."}}, {"id": "method-2", "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": 0.8, "band": "high", "quote": "DESeq2"}}, {"id": "method-3", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "χ 2"}}, {"id": "method-4", "family": "contingency_analysis", "specific": "fisher_exact", "label": "Categorical (contingency table) analysis", "dsl_operations": ["contingency_table", "chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "Fisher's exact"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "chi_square_test", "expected_value": 0.029, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": []}, "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": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "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": ["GSE111414", "GSE136961"], "resolved_accessions": ["GSE111414", "GSE136961"], "statements": ["The original contributions presented in the study are included in the article/Supplementary Materials, and further enquiries can be directed to the corresponding authors."], "basis": "The paper names GSE111414, GSE136961 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:38558529", "data:geo:GSE111414"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE111414"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:14:22Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9926, "completion_tokens": 2141, "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:38558529", "type": "paper", "label": "pmid:38558529"}, {"id": "source:pmid:38558529", "type": "manuscript", "label": "PMID 38558529 full text"}, {"id": "data:geo:GSE111414", "type": "dataset", "label": "GEO GSE111414"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38558529", "type": "paper", "label": "pmid:38558529"}, {"id": "source:pmid:38558529", "type": "manuscript", "label": "PMID 38558529 full text"}, {"id": "data:geo:GSE111414", "type": "dataset", "label": "GEO GSE111414"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38558529", "type": "extraction", "used": ["source:pmid:38558529"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE111414", "type": "accession_resolution", "used": ["data:geo:GSE111414"], "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:38558529", "parent_hash": "sha256:8f7afbf2bcddba3b2b24f7bd1e440c80b783d21f848a1110cfb314641b85d250", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE111414 licence not read", "asset:data:geo:GSE111414 not downloaded", "asset:data:geo:GSE136961 licence not read", "asset:data:geo:GSE136961 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Results from univariate and multivariate Cox regression for OS showed that TLS‐positive was an independent protective factor (Table S3)."], "order_basis": "analysis_only", "id": "assay:1"}]}