TREM1 promotes cancer associated malignant phenotype through activated MAPK signaling pathway and predicts poor prognosis in gastric cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38449634", "kind": "science-record", "revision": 4, "content_hash": "sha256:3b863e3f0b1cae7a66a15929ce410f146fa14c64f6f0dd957af87fb17e53cbd8", "created_at": "2026-11-01T19:20:23Z", "updated_at": "2026-11-01T22:53:49Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "TREM1 promotes cancer associated malignant phenotype through activated MAPK signaling pathway and predicts poor prognosis in gastric cancer.", "doi": "10.1016/j.heliyon.2024.e26852", "pmid": "38449634", "authors": ["Long Chen", "Fen Huang", "Xiaopan Luo", "Zan Chen"], "journal": "Heliyon", "year": 2024, "abstract": "Background: CD molecules plays a vital role in gastric cancer (GC). We used bioinformatics analysis methods to develop prognosis related CD molecules risk signature; On the other hand, we used the experiments to further explore the function and mechanism of differentially expressed prognostic CD molecules (TREM1) in GC.\nMethods: Kaplan-Meier survival and univariate Cox regression analysis were used to evaluate the overall survival of CD molecule genes in gastric cancer. ROC curve and Kaplan-Meier curves were used to analyze the predictive value of CD molecule related genes risk signature by \"survival and timeROC\" R packages. GSEA, and Cibersortx software were used to analyze the functional enrichment. Finally, we verified the function and mechanism of TREM1 in GC by gene silencing and MAPK inhibitor (SB203580) in vitro and vivo.\nResults: A total of 41 prognosis related risk factors in gastric cancer were identified based on CD molecules, including TREM1 and ect. The high-risk patients had higher risk score and shorter survival time. ROC curves revealed that this risk signature accurately predicted survival times of gastric cancer patients at the 1-, 2-, 3-, 4- and 5-year. The frequency of T cells follicular helper and NK cells activated were added in low-risk group. Next, differentially expressed prognostic CD molecules analysis revealed that TREM1 was identified as key genes in GC progression based on TCGA and GES158662 and GSE15459 datasets of GC. In vitro experiments, TREM1 silencing significantly inhibited GC cell proliferation and migration, induced cell apoptosis. GSEA revealed that TREM1 activated cancer related signaling pathway, including MAPK signaling pathway and ect. High expression of TREM1 was related Macrophages M2 and Mast cells resting in GC tissues. Moreover, knockdown of TREM1 inhibited tumor growth through downregulated MAPK signaling pathway in vivo.\nConclusion: These results identified that CD molecule related genes as a novel prognostic and diagnostic biomarker in gastric cancer. TREM1 acts as an oncogene role in GC by activated MAPK signaling pathway.", "claims": [{"id": "claim-method", "statement": "Kaplan-Meier survival and univariate Cox regression analysis was used to evaluate the overall survival of CD molecule in gastric cancer.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38449634", "locator": "sections[4] \"Prognosis related CD molecules genes\" paragraph 2", "quote": "Kaplan-Meier survival and univariate Cox regression analysis was used to evaluate the overall survival of CD molecule in gastric cancer."}], "state": "complete"}, {"id": "claim-data-access", "statement": "GSE158662, GSE103236, GSE15459 dataset was downloaded from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/gds/). Data will be made available on request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38449634", "locator": "sections[30] \"Data availability statement\" paragraph 2", "quote": "GSE158662, GSE103236, GSE15459 dataset was downloaded from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/gds/). Data will be made available on request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Kaplan-Meier survival and univariate Cox regression analysis were used to evaluate the overall survival of CD molecule in gastric cancer.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38449634", "locator": "sections[4] \"Prognosis related CD molecules genes\" paragraph 2", "quote": "Kaplan-Meier survival and univariate Cox regression analysis was used to evaluate the overall survival of CD molecule in gastric cancer."}, {"asset": "source:pmid:38449634", "locator": "sections[19] \"Identification of prognosis related risk factors in gastric cancer based on CD molecules\" paragraph 2", "quote": "A total of 41 prognosis related CD molecules were acquired from 422 CD molecules in gastric cancer (Supplemental Fig. 1)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Kaplan-Meier survival and univariate Cox regression analysis were used to evaluate the overall survival of CD molecule in gastric cancer.", "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:38449634"], "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:GSE103236"], "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:GSE103236"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38449634", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.heliyon.2024.e26852", "sha256": "sha256:99f6b68136e589a52d1cd4090b2eed123d16db77de3ef9ea898cc799c3111bd0", "bytes": 36153, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.heliyon.2024.e26852", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10915522", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE103236", "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=GSE103236", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE103236", "version": null, "note": "GSE158662, GSE103236, GSE15459 dataset was downloaded from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/gds/). Data will be made available on request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "GSE158662, GSE103236, GSE15459 dataset was downloaded from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/gds/). Data will be made available on request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2758660", "GSM2758661", "GSM2758662", "GSM2758663", "GSM2758664", "GSM2758665", "GSM2758666", "GSM2758667", "GSM2758668", "GSM2758669", "GSM2758670", "GSM2758671", "GSM2758672", "GSM2758673", "GSM2758674", "GSM2758675", "GSM2758676", "GSM2758677", "GSM2758678"], "sample_count": 19, "group_sizes": null, "group_sizes_basis": null, "platform": "4133", "taxon": "Homo sapiens", "title": "Microarray gene expresion analysis for early and advanced gastric adenocarcinoma vs normal adjacent tissue.", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE15459", "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=GSE15459", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE15459", "version": null, "note": "GSE158662, GSE103236, GSE15459 dataset was downloaded from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/gds/). Data will be made available on request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "GSE158662, GSE103236, GSE15459 dataset was downloaded from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/gds/). Data will be made available on request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM387788", "GSM387789", "GSM387790", "GSM387791", "GSM387792", "GSM387793", "GSM387794", "GSM387795", "GSM387796", "GSM387797", "GSM387798", "GSM387799", "GSM387800", "GSM387801", "GSM387802", "GSM387803", "GSM387804", "GSM387805", "GSM387806", "GSM387807", "GSM387808", "GSM387809", "GSM387810", "GSM387811", "GSM387812", "GSM387813", "GSM387814", "GSM387815", "GSM387816", "GSM387817", "GSM387818", "GSM387819", "GSM387820", "GSM387821", "GSM387822", "GSM387823", "GSM387824", "GSM387825", "GSM387826", "GSM387827", "GSM387828", "GSM387829", "GSM387830", "GSM387831", "GSM387832", "GSM387833", "GSM387834", "GSM387835", "GSM387836", "GSM387837", "GSM387838", "GSM387839", "GSM387840", "GSM387841", "GSM387842", "GSM387843", "GSM387844", "GSM387845", "GSM387846", "GSM387847", "GSM387848", "GSM387849", "GSM387850", "GSM387851", "GSM387852", "GSM387853", "GSM387854", "GSM387855", "GSM387856", "GSM387857", "GSM387858", "GSM387859", "GSM387860", "GSM387861", "GSM387862", "GSM387863", "GSM387864", "GSM387865", "GSM387866", "GSM387867", "GSM387868", "GSM387869", "GSM387870", "GSM387871", "GSM387872", "GSM387873", "GSM387874", "GSM387875", "GSM387876", "GSM387877", "GSM387878", "GSM387879", "GSM387880", "GSM387881", "GSM387882", "GSM387883", "GSM387884", "GSM387885", "GSM387886", "GSM387887", "GSM387888", "GSM387889", "GSM387890", "GSM387891", "GSM387892", "GSM387893", "GSM387894", "GSM387895", "GSM387896", "GSM387897", "GSM387898", "GSM387899", "GSM387900", "GSM387901", "GSM387902", "GSM387903", "GSM387904", "GSM387905", "GSM387906", "GSM387907", "GSM387908", "GSM387909", "GSM387910", "GSM387911", "GSM387912", "GSM387913", "GSM387914", "GSM387915", "GSM387916", "GSM387917", "GSM387918", "GSM387919", "GSM387920", "GSM387921", "GSM387922", "GSM387923", "GSM387924", "GSM387925", "GSM387926", "GSM387927", "GSM387928", "GSM387929", "GSM387930", "GSM387931", "GSM387932", "GSM387933", "GSM387934", "GSM387935", "GSM387936", "GSM387937", "GSM387938", "GSM387939", "GSM387940", "GSM387941", "GSM387942", "GSM387943", "GSM387944", "GSM387945", "GSM387946", "GSM387947", "GSM387948", "GSM387949", "GSM387950", "GSM387951", "GSM387952", "GSM387953", "GSM387954", "GSM387955", "GSM387956", "GSM387957", "GSM387958", "GSM387959", "GSM387960", "GSM387961", "GSM387962", "GSM387963", "GSM387964", "GSM387965", "GSM387966", "GSM387967", "GSM387968", "GSM387969", "GSM387970", "GSM387971", "GSM387972", "GSM387973", "GSM387974", "GSM387975", "GSM387976", "GSM387977", "GSM387978", "GSM387979", "GSM387980", "GSM387981", "GSM387982", "GSM387983", "GSM387984", "GSM387985", "GSM387986", "GSM387987"], "sample_count": 200, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gastric Cancer Project '08 (Singapore Patient Cohort)", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE158662", "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=GSE158662", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE158662", "version": null, "note": "GSE158662, GSE103236, GSE15459 dataset was downloaded from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/gds/). Data will be made available on request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "GSE158662, GSE103236, GSE15459 dataset was downloaded from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/gds/). Data will be made available on request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4805171", "GSM4805172", "GSM4805173", "GSM4805174", "GSM4805175", "GSM4805176"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "22755", "taxon": "Homo sapiens", "title": "mRNA expression of gastric cancer and paracancerous tissues", "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:GSE103236 not downloaded", "asset:data:geo:GSE103236 licence not read", "asset:data:geo:GSE15459 not downloaded", "asset:data:geo:GSE15459 licence not read", "asset:data:geo:GSE158662 not downloaded", "asset:data:geo:GSE158662 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "Kaplan-Meier survival and univariate Cox regression analysis was used to evaluate the overall survival of CD molecule in gastric cancer."}}, {"id": "method-2", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Student's t-test"}}, {"id": "method-3", "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": 0.8, "band": "high", "quote": "ANOVA"}}, {"id": "method-4", "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-5", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.7, "band": "medium", "quote": "ROC curve"}}], "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": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "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": ["GSE158662", "GSE103236", "GSE15459"], "resolved_accessions": ["GSE158662", "GSE103236", "GSE15459"], "statements": ["GSE158662, GSE103236, GSE15459 dataset was downloaded from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/gds/). Data will be made available on request."], "basis": "The paper names GSE158662, GSE103236, GSE15459 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": ["survival_km"], "assets": ["source:pmid:38449634", "data:geo:GSE103236"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE103236"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:10:56Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10778, "completion_tokens": 1891, "cached_tokens": 256}}, "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:38449634", "type": "paper", "label": "pmid:38449634"}, {"id": "source:pmid:38449634", "type": "manuscript", "label": "PMID 38449634 full text"}, {"id": "data:geo:GSE103236", "type": "dataset", "label": "GEO GSE103236"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38449634", "type": "paper", "label": "pmid:38449634"}, {"id": "source:pmid:38449634", "type": "manuscript", "label": "PMID 38449634 full text"}, {"id": "data:geo:GSE103236", "type": "dataset", "label": "GEO GSE103236"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38449634", "type": "extraction", "used": ["source:pmid:38449634"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE103236", "type": "accession_resolution", "used": ["data:geo:GSE103236"], "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:38449634", "parent_hash": "sha256:b2d209290c5e220230d4610e27990a347aecb05ff7a4ec0278edd5580cbf7fbf", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE103236 licence not read", "asset:data:geo:GSE103236 not downloaded", "asset:data:geo:GSE15459 licence not read", "asset:data:geo:GSE15459 not downloaded", "asset:data:geo:GSE158662 licence not read", "asset:data:geo:GSE158662 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["ll proliferation and migration, induced cell apoptosis. GSEA revealed that TREM1 activated cancer r"], "order_basis": "paper_text_order:1682", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["Mast cells resting in GC tissues. Moreover, knockdown of TREM1 inhibited tumor growth through down"], "order_basis": "paper_text_order:1905", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["through downregulated MAPK signaling pathway in vivo. Conclusion: These results identified that C"], "order_basis": "paper_text_order:1991", "id": "assay:3"}, {"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": ["oresource Center (ATCC, USA). The cells were cultured in RPMI-1640 medium (Gibco, USA) added with 10%"], "order_basis": "paper_text_order:2637", "id": "assay:4"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Kaplan-Meier survival and univariate Cox regression analysis was used to evaluate the overall survival of CD molecule in gastric cancer."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}