Potential association of LOXL1 with peritoneal dissemination in gastric cancer possibly via promotion of EMT.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33095806", "kind": "science-record", "revision": 8, "content_hash": "sha256:c1744cb84e10fc9bd74b2f6f26385c58f4d36310d5dcd62375def5a5113091b9", "created_at": "2026-11-01T15:41:13Z", "updated_at": "2026-11-01T22:02:23Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Potential association of LOXL1 with peritoneal dissemination in gastric cancer possibly via promotion of EMT.", "doi": "10.1371/journal.pone.0241140", "pmid": "33095806", "authors": ["Qingjiang Hu", "Takaaki Masuda", "Shotaro Kuramitsu", "Taro Tobo", "Kuniaki Sato", "Shinya Kidogami", "Sho Nambara", "Masami Ueda", "Yusuke Tsuruda", "Yosuke Kuroda", "Shuhei Ito", "Eiji Oki", "Masaki Mori", "Koshi Mimori"], "journal": "PloS one", "year": 2020, "abstract": "BACKGROUND: Peritoneal dissemination (PD) frequently occurs in gastric cancer (GC) and is incurable. In this study, we aimed to identify novel PD-associated genes and clarify their clinical and biological significance in GC.\nMATERIALS AND METHODS: We identified LOXL1 as a PD-associated candidate gene by in silico analysis of GC datasets (highly disseminated peritoneal GC cell line and two freely available GC datasets, GSE15459 and TCGA). Next, we evaluated the clinical significance of LOXL1 expression using RT-qPCR and immunohistochemistry staining (IHC) in a validation cohort (Kyushu cohort). Moreover, we performed gene expression analysis, including gene set enrichment analysis (GSEA) with GSE15459 and TCGA datasets. Finally, we performed a series of in vitro experiments using GC cells.\nRESULTS: In silico analysis showed that LOXL1 was overexpressed in tumor tissues of GC patients with PD and in highly disseminated peritoneal GC cells, relative to that in the control GC patients and cells, respectively. High expression of LOXL1 was a poor prognostic factor in the TCGA dataset. Next, IHC showed that LOXL1 was highly expressed in GC cells. High LOXL1 mRNA expression was associated with poorly differentiated histological type, lymph node metastasis, and was an independent poor prognostic factor in the Kyushu validation cohort. Moreover, LOXL1 expression was positively correlated with the EMT (epithelial-mesenchymal transition) gene set in GSEA. Finally, LOXL1-overexpressing GC cells changed their morphology to a spindle-like form. LOXL1 overexpression reduced CDH1 expression; increased the expression of VIM, CDH2, SNAI2, and PLS3; and promoted the migration capacity of GC cells.\nCONCLUSIONS: LOXL1 is associated with PD in GC, possibly through the induction of EMT.", "claims": [{"id": "claim-data-access", "statement": "We obtained mRNA expression data and clinical assessments of 238 GC patients from the Broad Institute’s Firehose (http://gdac.broadinstitute.org/runs/stddata__2015_06_01/data/STAD/20150601/)). The mRNA expression data (RPKM, raw count) from 238 tumor and 33 normal tissues were normalized with quantile normalization. Clinical data were available from 223 patients.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33095806", "locator": "sections[3] \"TCGA dataset\" paragraph 2", "quote": "We obtained mRNA expression data and clinical assessments of 238 GC patients from the Broad Institute’s Firehose (http://gdac.broadinstitute.org/runs/stddata__2015_06_01/data/STAD/20150601/)). The mRNA expression data (RPKM, raw count) from 238 tumor and 33 normal tissues were normalized with quantile normalization. Clinical data were available from 223 patients."}], "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:33095806"], "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:GSE15459"], "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:GSE15459"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33095806", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0241140", "sha256": "sha256:f1666c8957571d4b9d7733ef8c543cd506326782964da5b41ef9e40bfc60e4af", "bytes": 30781, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1371/journal.pone.0241140", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7584171", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"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": "We obtained mRNA expression data and clinical assessments of 238 GC patients from the Broad Institute’s Firehose (http://gdac.broadinstitute.org/runs/stddata__2015_06_01/data/STAD/20150601/)). The mRNA expression data (RPKM, raw count) from 238 tumor and 33 normal tissues were normalized with quantile normalization. Clinical data were available from 223 patients.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "We obtained mRNA expression data and clinical assessments of 238 GC patients from the Broad Institute’s Firehose (http://gdac.broadinstitute.org/runs/stddata__2015_06_01/data/STAD/20150601/)). The mRNA expression data (RPKM, raw count) from 238 tumor and 33 normal tissues were normalized with quantile normalization. Clinical data were available from 223 patients.", "access_statement_kind": "repository_route_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": "asset:table:pmid:33095806:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:207c63861a41d73e91dc1b307e59200f94e0431c07726d4bee751a669680c60f", "bytes": 271, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[19]/table-wrap[1]#pone.0241140.t001", "version": null, "note": "LOXL1 mRNA expression and clinicopathological factors of GC cases in the Kyushu validation cohort (n = 144).", "structure": {"pmcid": "PMC7584171", "section_index": 19, "section_title": "Clinicopathological analysis of LOXL1 expression in Kyushu validation cohort", "row_count": 0, "column_count": 0}, "table": {"label": "Table 1", "caption": "LOXL1 mRNA expression and clinicopathological factors of GC cases in the Kyushu validation cohort (n = 144).", "rows": [], "row_count": 0, "column_count": 0, "numeric_cells": 0, "header_rows": 0, "locator": "section[19]/table-wrap[1]#pone.0241140.t001"}}, {"id": "asset:table:pmid:33095806:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:9f9c6cad6a41a4ecedd83776c3f0fd15dd8f91f2a4e11cee833bab9436b7314b", "bytes": 314, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[20]/table-wrap[1]#pone.0241140.t002", "version": null, "note": "Univariate and multivariate analyses of clinicopathological factors affecting overall survival in GC cases from the Kyushu validation cohort (n = 144).", "structure": {"pmcid": "PMC7584171", "section_index": 20, "section_title": "Prognostic analysis of LOXL1 expression in Kyushu validation cohort", "row_count": 0, "column_count": 0}, "table": {"label": "Table 2", "caption": "Univariate and multivariate analyses of clinicopathological factors affecting overall survival in GC cases from the Kyushu validation cohort (n = 144).", "rows": [], "row_count": 0, "column_count": 0, "numeric_cells": 0, "header_rows": 0, "locator": "section[20]/table-wrap[1]#pone.0241140.t002"}}], "gaps": ["asset:data:geo:GSE15459 not downloaded", "asset:data:geo:GSE15459 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 1.0, "band": "reordered", "quote": "“we calculated Pearson-Correlation between DNA copy number variation and mRNA expression of LOXL1 using a publicly available online portal, LinkedOmics, that includes multi-omics data from all 32 TCGA cancer types [28].”"}}, {"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": "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": 0.8, "band": "high", "quote": "Kaplan-Meier"}}, {"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": 0.8, "band": "high", "quote": "Cox regression"}}, {"id": "method-5", "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": ["pearson_r"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pearson."}, "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": ["GSE15459"], "resolved_accessions": ["GSE15459"], "statements": ["We obtained mRNA expression data and clinical assessments of 238 GC patients from the Broad Institute’s Firehose (http://gdac.broadinstitute.org/runs/stddata__2015_06_01/data/STAD/20150601/)). The mRNA expression data (RPKM, raw count) from 238 tumor and 33 normal tissues were normalized with quantile normalization. Clinical data were available from 223 patients."], "basis": "The paper names GSE15459 in Gene Expression Omnibus and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["pearson_r"], "assets": ["source:pmid:33095806", "data:geo:GSE15459", "asset:table:pmid:33095806:1", "asset:table:pmid:33095806:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE15459"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:23:34Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 24625, "completion_tokens": 2047, "cached_tokens": 540}}, "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:33095806", "type": "paper", "label": "pmid:33095806"}, {"id": "source:pmid:33095806", "type": "manuscript", "label": "PMID 33095806 full text"}, {"id": "data:geo:GSE15459", "type": "dataset", "label": "GEO GSE15459"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33095806", "type": "paper", "label": "pmid:33095806"}, {"id": "source:pmid:33095806", "type": "manuscript", "label": "PMID 33095806 full text"}, {"id": "data:geo:GSE15459", "type": "dataset", "label": "GEO GSE15459"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33095806", "type": "extraction", "used": ["source:pmid:33095806"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE15459", "type": "accession_resolution", "used": ["data:geo:GSE15459"], "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:33095806", "parent_hash": "sha256:399293b83e8b3a9b79ba4099ec9e344a36a5aaf83551cbe1e86a03380708b80b", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE15459 licence not read", "asset:data:geo:GSE15459 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": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["nical significance of LOXL1 expression using RT-qPCR and immunohistochemistry staining (IHC) in a", "al significance of LOXL1 expression using RT-qPCR and immunohistochemistry staining (IHC) in a", "analyzed LOXL1 expression by IHC (n = 5) and RT-qPCR (n = 144) in GC tissues of the Kyushu valida", "lyzed LOXL1 expression by IHC (n = 5) and RT-qPCR (n = 144) in GC tissues of the Kyushu valida"], "order_basis": "paper_text_order:578", "id": "assay:1"}, {"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": ["icance of LOXL1 expression using RT-qPCR and immunohistochemistry staining (IHC) in a validation cohort (Kyush", "g RT-qPCR and immunohistochemistry staining (IHC) in a validation cohort (Kyushu cohort). Mor", "prognostic factor in the TCGA dataset. Next, IHC showed that LOXL1 was highly expressed in GC", "tissues (Fig 2A and S1 Fig). Moreover, LOXL1 immunostaining intensity was positively associated with LOX"], "order_basis": "paper_text_order:590", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["and gathering cells from the ascites. These cell lines were cultured in RPMI 1640 (Gibco, CA, USA) supplemented w", "ells from the ascites. These cell lines were cultured in RPMI 1640 (Gibco, CA, USA) supplemented with"], "order_basis": "paper_text_order:4324", "id": "assay:3"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pearson_r"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["“we calculated Pearson-Correlation between DNA copy number variation and mRNA expression of LOXL1 using a publicly available online portal, LinkedOmics, that includes multi-omics data from all 32 TCGA cancer types [28].”"], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}