PRRX1-OLR1 axis supports CAFs-mediated lung cancer progression and immune suppression.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39010054", "kind": "science-record", "revision": 4, "content_hash": "sha256:13a1e8fa68b3ab7a2be839b33dce2fce8613c723fc5a33eae45d05094f1c16e8", "created_at": "2026-11-01T20:29:05Z", "updated_at": "2026-11-01T22:54:42Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "PRRX1-OLR1 axis supports CAFs-mediated lung cancer progression and immune suppression.", "doi": "10.1186/s12935-024-03436-9", "pmid": "39010054", "authors": ["Yunhao Sun", "Kaijun Ying", "Jian Sun", "Yao Wang", "Limin Qiu", "Mingming Ji", "Lin Sun", "Jinjin Chen"], "journal": "Cancer cell international", "year": 2024, "abstract": "OBJECTIVE: To investigate the mechanism by which cancer-associated fibroblasts (CAFs) affect the growth and immune evasion of lung cancer cells.\nMETHODS: Initially, datasets comparing CAFs with normal fibroblasts were downloaded from the GEO dataset GSE48397. Genes with the most significant differential expression were selected and validated using clinical data. Subsequently, CAFs were isolated, and the selected genes were knocked down in CAFs. Co-culture experiments were conducted with H1299 or A549 cells to analyze changes in lung cancer cell growth, migration, and immune evasion in vitro and in vivo. To further elucidate the upstream regulatory mechanism, relevant ChIP-seq data were downloaded from the GEO database, and the regulatory relationships were validated through ChIP-qPCR and luciferase reporter assays.\nRESULTS: OLR1 was significantly overexpressed in CAFs and strongly correlated with adverse prognosis in lung cancer patients. Knockdown of OLR1 markedly inhibited CAFs' support for the growth and immune evasion of lung cancer cells in vitro and in vivo. ChIP-seq results demonstrated that PRRX1 can promote OLR1 expression by recruiting H3K27ac and H3K4me3, thereby activating CAFs. Knockdown of PRRX1 significantly inhibited CAFs' function, while further overexpression of OLR1 restored CAFs' support for lung cancer cell growth, migration, and immune evasion.\nCONCLUSION: PRRX1 promotes OLR1 expression by recruiting H3K27ac and H3K4me3, activating CAFs, and thereby promoting the growth, migration, and immune evasion of lung cancer cells.", "claims": [{"id": "claim-method", "statement": "The data were assessed for normality using the Kolmogorov–Smirnov test, and as the data followed a normal distribution, results are presented as mean ± standard deviation. Comparisons between two groups were conducted using the t-test, while comparisons among multiple groups were analyzed using One-Way ANOVA (analysis of variance). Post hoc pairwise comparisons following ANOVA were conducted using Tukey's multiple comparisons test. Survival curves were generated using the Kaplan–Meier method, and statistical significance was assessed using the Log-rank test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39010054", "locator": "sections[20] \"Statistical analysis\" paragraph 2", "quote": "The data were assessed for normality using the Kolmogorov–Smirnov test, and as the data followed a normal distribution, results are presented as mean ± standard deviation. Comparisons between two groups were conducted using the t-test, while comparisons among multiple groups were analyzed using One-Way ANOVA (analysis of variance). Post hoc pairwise comparisons following ANOVA were conducted using Tukey's multiple comparisons test. Survival curves were generated using the Kaplan–Meier method, and statistical significance was assessed using the Log-rank test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data will be made available on request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39010054", "locator": "sections[35] \"Data availability\" paragraph 2", "quote": "Data will be made available on request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "PRRX1 promotes OLR1 expression by recruiting H3K27ac and H3K4me3, activating CAFs, and thereby promoting the growth, migration, and immune evasion of lung cancer cells.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39010054", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "PRRX1 promotes OLR1 expression by recruiting H3K27ac and H3K4me3, activating CAFs, and thereby promoting the growth, migration, and immune evasion of lung cancer cells."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "PRRX1 promotes OLR1 expression by recruiting H3K27ac and H3K4me3, activating CAFs, and thereby promoting the growth, migration, and immune evasion of lung cancer cells.", "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:39010054"], "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:GSE240001"], "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:GSE240001"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39010054", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12935-024-03436-9", "sha256": "sha256:ca31d45a6da2a24b621ba0898426047130d5b68fc80e15256c766daf814cf06f", "bytes": 55964, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12935-024-03436-9", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11251326", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE240001", "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=GSE240001", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE240001", "version": null, "note": "Data will be made available on request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data will be made available on request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM7679652", "GSM7679653", "GSM7679654", "GSM7679655", "GSM7679656", "GSM7679657", "GSM7679658", "GSM7679659", "GSM7679660", "GSM7679661", "GSM7679662"], "sample_count": 11, "group_sizes": null, "group_sizes_basis": null, "platform": "24676", "taxon": "Homo sapiens", "title": "Phase Ib trial of inhaled iloprost for the prevention of lung cancer with predictive and response biomarker assessment response biomarker assessment (scRNA-Seq).", "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:GSE48397", "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=GSE48397", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE48397", "version": null, "note": "Data will be made available on request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data will be made available on request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1177015", "GSM1177016", "GSM1177017", "GSM1177018", "GSM1177019", "GSM1177020", "GSM1177021", "GSM1177022", "GSM1177023", "GSM1177024"], "sample_count": 10, "group_sizes": null, "group_sizes_basis": null, "platform": "1261", "taxon": "Mus musculus", "title": "Expression data from (mouse) normal lung fibroblasts and carcinoma-associated fibroblasts", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE240001 not downloaded", "asset:data:geo:GSE240001 licence not read", "asset:data:geo:GSE48397 not downloaded", "asset:data:geo:GSE48397 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The data were assessed for normality using the Kolmogorov–Smirnov test, and as the data followed a normal distribution, results are presented as mean ± standard deviation. Comparisons between two groups were conducted using the t-test, while comparisons among multiple groups were analyzed using One-Way ANOVA (analysis of variance). Post hoc pairwise comparisons following ANOVA were conducted using Tukey's multiple comparisons test. Survival curves were generated using the Kaplan–Meier method, and statistical significance was assessed using the Log-rank test."}}, {"id": "method-2", "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": []}, "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": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "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": ["GSE48397", "GSE240001"], "resolved_accessions": ["GSE48397", "GSE240001"], "statements": ["Data will be made available on request."], "basis": "The paper names GSE48397, GSE240001 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "assets": ["source:pmid:39010054", "data:geo:GSE240001"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE240001"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:24:03Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 15678, "completion_tokens": 1295, "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:39010054", "type": "paper", "label": "pmid:39010054"}, {"id": "source:pmid:39010054", "type": "manuscript", "label": "PMID 39010054 full text"}, {"id": "data:geo:GSE240001", "type": "dataset", "label": "GEO GSE240001"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39010054", "type": "paper", "label": "pmid:39010054"}, {"id": "source:pmid:39010054", "type": "manuscript", "label": "PMID 39010054 full text"}, {"id": "data:geo:GSE240001", "type": "dataset", "label": "GEO GSE240001"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39010054", "type": "extraction", "used": ["source:pmid:39010054"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE240001", "type": "accession_resolution", "used": ["data:geo:GSE240001"], "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:39010054", "parent_hash": "sha256:e0b7fd7e22534d1df9a9c1a4d01f1482a6409beb4d02735eec2dce87923fcea6", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE240001 licence not read", "asset:data:geo:GSE240001 not downloaded", "asset:data:geo:GSE48397 licence not read", "asset:data:geo:GSE48397 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["ure experiments were conducted with H1299 or A549 cells to analyze changes in lung cancer cell"], "order_basis": "paper_text_order:543", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": [", migration, and immune evasion in vitro and in vivo. To further elucidate the upstream regulator", "ne evasion of lung cancer cells in vitro and in vivo. ChIP-seq results demonstrated that PRRX1 ca", "eins of mice. Starting from the second week, mice were treated with anti-PD-1 therapy (50 mg/kg/wee", "(50 mg/kg/week) for 8 weeks, after which the mice were euthanized. Tumor nodules formed on the lung"], "order_basis": "paper_text_order:644", "id": "assay:2"}, {"role": "data_generation", "definition_id": "chip_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["the upstream regulatory mechanism, relevant ChIP-seq data were downloaded from the GEO database,", "n of lung cancer cells in vitro and in vivo. ChIP-seq results demonstrated that PRRX1 can promote"], "order_basis": "paper_text_order:719", "id": "assay:3"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ry relationships were validated through ChIP-qPCR and luciferase reporter assays. RESULTS: OLR", "H–I Quantitative polymerase chain reaction (qPCR) and Western blot (WB) analyses revealing OL"], "order_basis": "paper_text_order:832", "id": "assay:4"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["h adverse prognosis in lung cancer patients. Knockdown of OLR1 markedly inhibited CAFs' support for", "3K27ac and H3K4me3, thereby activating CAFs. Knockdown of PRRX1 significantly inhibited CAFs' funct"], "order_basis": "paper_text_order:995", "id": "assay:5"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["nely dehydrated and embedded in paraffin for immunohistochemistry (IHC) analysis. Clinical information for all", "ning intensity and patient prognosis through immunohistochemistry (IHC). We observed that patients with higher", "ating specific expression of OLR1 in CAFs. E Immunohistochemistry (IHC) analysis of OLR1 staining intensity in", "ancer tissues using enzymatic digestion, and immunofluorescence analysis confirmed the positive expression o"], "order_basis": "paper_text_order:1884", "id": "assay:6"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["g to analyze the number of lung nodules, and flow cytometry was used to assess the proportion of immune"], "order_basis": "paper_text_order:2810", "id": "assay:7"}, {"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["overexpression in CAFs. C UMAP clustering of single-cell RNA-seq data from the dataset GSE240001, showing dim"], "order_basis": "paper_text_order:5612", "id": "assay:8"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["on in CAFs. C UMAP clustering of single-cell RNA-seq data from the dataset GSE240001, showing dim"], "order_basis": "paper_text_order:5624", "id": "assay:9"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["itative polymerase chain reaction (qPCR) and Western blot (WB) analyses revealing OLR1 mRNA and protei"], "order_basis": "paper_text_order:6413", "id": "assay:10"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The data were assessed for normality using the Kolmogorov–Smirnov test, and as the data followed a normal distribution, results are presented as mean ± standard deviation. Comparisons between two groups were conducted using the t-test, while comparisons among multiple groups were analyzed using One-Way ANOVA (analysis of variance). Post hoc pairwise comparisons following ANOVA were conducted using Tukey's multiple comparisons test. Survival curves were generated using the Kaplan–Meier method, and statistical significance was assessed using the Log-rank test."], "order_basis": "consumes_earlier_output", "id": "assay:11"}]}