12-Chemokine signature, a predictor of tumor recurrence in colorectal cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32191346", "kind": "science-record", "revision": 4, "content_hash": "sha256:ba4f0caa22f287b91aff0d3dea4f2cc09a27fb17afe3516f7428a3aa05a849e9", "created_at": "2026-11-01T17:33:28Z", "updated_at": "2026-11-01T22:44:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "12-Chemokine signature, a predictor of tumor recurrence in colorectal cancer.", "doi": "10.1002/ijc.32982", "pmid": "32191346", "authors": ["Ryuma Tokunaga", "Shigeki Nakagawa", "Yasuo Sakamoto", "Kenichi Nakamura", "Madiha Naseem", "Daisuke Izumi", "Keisuke Kosumi", "Katsunobu Taki", "Takaaki Higashi", "Tatsunori Miyata", "Yuji Miyamoto", "Naoya Yoshida", "Hideo Baba", "Heinz-Josef Lenz"], "journal": "International journal of cancer", "year": 2020, "abstract": "Tertiary lymphoid structures (TLSs) provide an immunological antineoplastic effect. Recent evidences link a unique 12-chemokine (CCL2, -3, -4, -5, -8, -18, -19, -21, CXCL9, -10, -11, -13) signature status from tumor tissue and the TLS expression. However, the potential significance of 12-chemokine signature status for clinical use is unknown. We aimed to evaluate the association of 12-chemokine signature status with patient outcomes in colorectal cancer (CRC). We used integrated data of resected 975 CRC cases within three independent cohorts from France, Japan and the United States (GSE39582, KUMAMOTO from Kumamoto university hospital and TCGA). The association of 12-chemokine signature status with clinicopathological features, patient outcome, TLS expression status and key tumor molecular features was analyzed. Patients with low 12-chemokine signature status had a significant shorter relapse-free survival in discovery cohort (HR: 1.61, 95% CI: 1.11-2.39, p = 0.0123), which was confirmed in validation cohort (HR: 3.31, 95% CI: 1.33-10.08, p = 0.0087). High 12-chemokine signature status had significant associations with right-sided tumor, high tumor-localized TLS expression, BRAF mutant, CIMP-high status and MSI-high status. Furthermore, RNA-seq based analysis showed that high 12-chemokine signature status was strongly associated with inflammation-related, immune cells-related and apoptosis pathways (using gene set enrichment analysis), and more tumor-infiltrating immune cells, such as cytotoxic T lymphocytes and myeloid dendritic cells (using MCP-counter analysis). We investigated a promising effect of 12-chemokine signature status in CRC patients who underwent resection. Our data may be helpful in developing novel immunological treatment strategies for CRC.", "claims": [{"id": "claim-method", "statement": "12-Chemokine signature was calculated by the 12 gene enrichment analysis based on mRNA expression level of each 12-chemokine,12,20 and the cases were categorized into high 12-chemokine (highest tertile) or low 12-chemokine (middle–lowest tertile) signature status in each cohort. The Kaplan–Meier plots and log-rank tests were performed to evaluate patient outcomes. Multivariate Cox proportional hazards regression model initially included sex (male vs. female), age (≤65 vs. >65), tumor location (right side vs. left side) and TNM stage (0–I vs. II vs. III vs. IV) to re-evaluate the independent effect of 12-chemokine signature status for OS and RFS.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32191346", "locator": "sections[5] \"Statistical analysis\" paragraph 2", "quote": "12-Chemokine signature was calculated by the 12 gene enrichment analysis based on mRNA expression level of each 12-chemokine,12,20 and the cases were categorized into high 12-chemokine (highest tertile) or low 12-chemokine (middle–lowest tertile) signature status in each cohort."}, {"asset": "source:pmid:32191346", "locator": "sections[5] \"Statistical analysis\" paragraph 2", "quote": "The Kaplan–Meier plots and log-rank tests were performed to evaluate patient outcomes."}, {"asset": "source:pmid:32191346", "locator": "sections[5] \"Statistical analysis\" paragraph 2", "quote": "Multivariate Cox proportional hazards regression model initially included sex (male vs. female), age (≤65 vs. >65), tumor location (right side vs. left side) and TNM stage (0–I vs."}, {"asset": "source:pmid:32191346", "locator": "sections[5] \"Statistical analysis\" paragraph 2", "quote": "II vs."}, {"asset": "source:pmid:32191346", "locator": "sections[5] \"Statistical analysis\" paragraph 2", "quote": "III vs."}, {"asset": "source:pmid:32191346", "locator": "sections[5] \"Statistical analysis\" paragraph 2", "quote": "IV) to re-evaluate the independent effect of 12-chemokine signature status for OS and RFS."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. For published datasets, the raw and processed RNA-seq data from frozen tissues are available through NCBI’s Gene Expression Omnibus (accession number GSE39582: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39582) and cBioportal website (“TCGA, Nature 2012” dataset: https://www.cbioportal.org/).22", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32191346", "locator": "sections[6] \"Data availability\" paragraph 2", "quote": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. For published datasets, the raw and processed RNA-seq data from frozen tissues are available through NCBI’s Gene Expression Omnibus (accession number GSE39582: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39582) and cBioportal website (“TCGA, Nature 2012” dataset: https://www.cbioportal.org/).22"}], "state": "complete"}, {"id": "claim-target-result", "statement": "Patients with low 12-chemokine signature status had a significant shorter relapse-free survival in discovery cohort (HR: 1.61, 95% CI: 1.11–2.39, p = 0.0123), which was confirmed in validation cohort (HR: 3.31, 95% CI: 1.33–10.08, p = 0.0087).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Patients with low 12-chemokine signature status had a significant shorter relapse-free survival in discovery cohort (HR: 1.61, 95% CI: 1.11–2.39, p = 0.0123), which was confirmed in validation cohort (HR: 3.31, 95% CI: 1.33–10.08, p = 0.0087)."}, "evidence": [{"asset": "source:pmid:32191346", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Patients with low 12-chemokine signature status had a significant shorter relapse-free survival in discovery cohort (HR: 1.61, 95% CI: 1.11–2.39, p = 0.0123), which was confirmed in validation cohort (HR: 3.31, 95% CI: 1.33–10.08, p = 0.0087)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Patients with low 12-chemokine signature status had a significant shorter relapse-free survival in discovery cohort (HR: 1.61, 95% CI: 1.11–2.39, p = 0.0123), which was confirmed in validation cohort (HR: 3.31, 95% CI: 1.33–10.08, p = 0.0087).", "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:32191346"], "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:GSE39582"], "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:GSE39582"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32191346", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1002/ijc.32982", "sha256": "sha256:9a58c214cc0ccd856660a9b8d9454a7bded09fd5533fb084bdd3f60695860fa7", "bytes": 27036, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1002/ijc.32982", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9371443", "source": "ncbi_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE39582", "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=GSE39582", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE39582", "version": null, "note": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. For published datasets, the raw and processed RNA-seq data from frozen tissues are available through NCBI’s Gene Expression Omnibus (accession number GSE39582: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39582) and cBioportal website (“TCGA, Nature 2012” dataset: https://www.cbioportal.org/).22", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. 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The Kaplan–Meier plots and log-rank tests were performed to evaluate patient outcomes. Multivariate Cox proportional hazards regression model initially included sex (male vs. female), age (≤65 vs. >65), tumor location (right side vs. left side) and TNM stage (0–I vs. II vs. III vs. IV) to re-evaluate the independent effect of 12-chemokine signature status for OS and RFS."}}, {"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"}}, {"id": "method-3", "family": "regression_modelling", "specific": "logistic", "label": "Regression modelling", "dsl_operations": ["glm_logit_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictors_and_outcome"], "evidence": {"score": 0.8, "band": "high", "quote": "logistic regression"}}, {"id": "method-4", "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": "chi-square"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "chi_square_test", "expected_value": 95.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}], "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": ["GSE39582"], "resolved_accessions": ["GSE39582"], "statements": ["The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. For published datasets, the raw and processed RNA-seq data from frozen tissues are available through NCBI’s Gene Expression Omnibus (accession number GSE39582: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39582) and cBioportal website (“TCGA, Nature 2012” dataset: https://www.cbioportal.org/).22"], "basis": "The paper names GSE39582 in NCBI’s Gene Expression Omnibus and the accession resolves in the repository. 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Furthermore, RNA-seq based analysis showed that high 12-chemokine", "tps://software.broadinstitute.org/morpheus/. RNA-seq based estimation of tumor infiltrating immun"], "order_basis": "paper_text_order:1290", "id": "assay:1"}, {"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": ["flammation-related, immune cells-related and apoptosis pathways (using gene set enrichment analysis"], "order_basis": "paper_text_order:1436", "id": "assay:2"}, {"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": ["12-Chemokine signature was calculated by the 12 gene enrichment analysis based on mRNA expression level of each 12-chemokine,12,20 and the cases were categorized into high 12-chemokine (highest tertile) or low 12-chemokine (middle–lowest tertile) signature status in each cohort. The Kaplan–Meier plots and log-rank tests were performed to evaluate patient outcomes. Multivariate Cox proportional hazards regression model initially included sex (male vs. female), age (≤65 vs. >65), tumor location (right side vs. left side) and TNM stage (0–I vs. II vs. III vs. IV) to re-evaluate the independent effect of 12-chemokine signature status for OS and RFS."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}