Identification of epigenetic silencing of the SFRP2 gene in colorectal cancer as a clinical biomarker and molecular significance.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38802858", "kind": "science-record", "revision": 4, "content_hash": "sha256:b4ab4f7dd8d8139084b148ec1eb022d76f4be742baff1b960e644633ad2d7366", "created_at": "2026-11-01T19:20:45Z", "updated_at": "2026-11-01T22:54:23Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of epigenetic silencing of the SFRP2 gene in colorectal cancer as a clinical biomarker and molecular significance.", "doi": "10.1186/s12967-024-05329-x", "pmid": "38802858", "authors": ["Hatim Boughanem", "Jesús Pilo", "Libia Alejandra García-Flores", "Isabel Arranz", "María Ramos-Fernandez", "María Ortega-Castan", "Ana B Crujeiras", "Juan Sandoval", "Manuel Macias-Gonzalez"], "journal": "Journal of translational medicine", "year": 2024, "abstract": "BACKGROUND: Several studies have suggested secreted frizzled-related protein 2 (SFRP2) gene as a potential clinical biomarker in colorectal cancer (CRC). However, its diagnostic role remains unclear. In this study, we aimed to investigate the significance of SFRP2 methylation levels in a large cohort of biological specimens (including blood, adipose and colonic tissues) from patients with CRC, thereby potentially identifying new biomarker utility.\nMETHODS: We examined the expression (by qPCR) and methylation status (by 450 K DNA array and DNA pyrosequencing) of the SFRP2 gene in healthy participants (N = 110, aged as 53.7 (14.2), 48/62 males/females) and patients with CRC (N = 85, aged 67.7 (10.5), 61/24 males/females), across different biological tissues, and assessing its potential as a biomarker for CRC. Additionally, we investigated the effect of recombinant human SFRP2 (rhSFRP2) as a therapeutic target, on cell proliferation, migration, and the expression of key genes related to carcinogenesis and the Wnt pathway.\nRESULTS: Our findings revealed that SFRP2 promoter methylation in whole blood could predict cancer stage (I + II vs. III + IV) (AUC = 0.653), lymph node invasion (AUC = 0.692), and CRC recurrence (AUC = 0.699) in patients with CRC (all with p < 0.05). Furthermore, we observed a global hypomethylation of SFRP2 in tumors compared to the adjacent area (p < 0.001). This observation was validated in the TCGA-COAD and TCGA-READ cohorts, demonstrating overall hypermethylation (both with p < 0.001) and low expression (p < 0.001), as shown in publicly available scRNA-Seq data. Notably, neoadjuvant-treated CRC patients exhibited lower SFRP2 methylation levels compared to untreated patients (p < 0.05) and low promoter SFRP2 methylation in untreated patients was associated with poor overall survival (p < 0.05), when compared to high methylation. Finally, treatment with 5 µg of rhSFRP2 treatment in CRC cells (HCT116 cells) inhibited cell proliferation (p < 0.001) and migration (p < 0.05), and downregulated the expression of AXIN2 (p < 0.01), a gene involved in Wnt signaling pathway.\nCONCLUSIONS: These findings establish promoter methylation of the SFRP2 gene as a prognostic candidate in CRC when assessed in blood, and as a therapeutic prognostic candidate in tumors, potentially valuable in clinical practice. SFRP2 also emerges as a therapeutic option, providing new clinical and therapeutical avenues.", "claims": [{"id": "claim-method", "statement": "Depending on the normality of the variables, either a Student’s t-test or a Wilcoxon test was used. Pearson correlation coefficients were calculated to evaluate the associations between methylation and anthropometric and biochemical parameters. Overall survival analyses were conducted using Kaplan–Meier curves, and multivariate proportional regression was used to calculate odds ratios (ORs) [95% confidence intervals (CIs)] and area under curve (AUC) for SFRP2 methylation adjusted by age, sex, BMI, HDL, triglycerides and cancer location. Logistic and linear regression analyses were conducted using SFRP2 promoter methylation in tumor, adjusted for age, sex and BMI.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38802858", "locator": "sections[14] \"Statistical analysis\" paragraph 2", "quote": "Depending on the normality of the variables, either a Student’s t-test or a Wilcoxon test was used. Pearson correlation coefficients were calculated to evaluate the associations between methylation and anthropometric and biochemical parameters. Overall survival analyses were conducted using Kaplan–Meier curves, and multivariate proportional regression was used to calculate odds ratios (ORs) [95% confidence intervals (CIs)] and area under curve (AUC) for SFRP2 methylation adjusted by age, sex, BMI, HDL, triglycerides and cancer location. Logistic and linear regression analyses were conducted using SFRP2 promoter methylation in tumor, adjusted for age, sex and BMI."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analyzed during the current study are not publicly available due the participants were anonymized but are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38802858", "locator": "sections[26] \"Availability of data and materials\" paragraph 2", "quote": "The datasets generated and/or analyzed during the current study are not publicly available due the participants were anonymized but are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Whole-blood SFRP2 promoter methylation was associated with colorectal cancer stage, lymph node invasion, and recurrence, while recombinant human SFRP2 reduced proliferation and migration in HCT116 colorectal cancer cells.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38802858", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Our findings revealed that SFRP2 promoter methylation in whole blood could predict cancer stage (I + II vs. III + IV) (AUC = 0.653), lymph node invasion (AUC = 0.692), and CRC recurrence (AUC = 0.699) in patients with CRC (all with p < 0.05)."}, {"asset": "source:pmid:38802858", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Finally, treatment with 5 µg of rhSFRP2 treatment in CRC cells (HCT116 cells) inhibited cell proliferation (p < 0.001) and migration (p < 0.05), and downregulated the expression of AXIN2 (p < 0.01), a gene involved in Wnt signaling pathway."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Whole-blood SFRP2 promoter methylation was associated with colorectal cancer stage, lymph node invasion, and recurrence, while recombinant human SFRP2 reduced proliferation and migration in HCT116 colorectal 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:38802858"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": ["The datasets generated and/or analyzed during the current study are not publicly available due the participants were anonymized but are available from the corresponding author on reasonable request."], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:38802858"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_wilcoxon", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:19:46Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 17027, "completion_tokens": 1830, "cached_tokens": 264}}, "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:38802858", "type": "paper", "label": "pmid:38802858"}, {"id": "source:pmid:38802858", "type": "manuscript", "label": "PMID 38802858 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38802858", "type": "paper", "label": "pmid:38802858"}, {"id": "source:pmid:38802858", "type": "manuscript", "label": "PMID 38802858 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38802858", "type": "extraction", "used": ["source:pmid:38802858"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "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:38802858", "parent_hash": "sha256:33acc566065865017be6303021265a19846cefdd3270da762995c79409b0ef1a", "fork_of": null, "generation": 3}, "gaps": ["execution.not_run", "method.group_comparison_wilcoxon", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent", "step:run_analysis blocked on method:group_comparison_wilcoxon"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ity. METHODS: We examined the expression (by qPCR) and methylation status (by 450 K DNA array"], "order_basis": "paper_text_order:577", "id": "assay:1"}, {"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": ["-247™) human colorectal carcinoma cells were cultured in Dulbecco’s Modified Eagle’s Medium—low gluco"], "order_basis": "paper_text_order:5572", "id": "assay:2"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Depending on the normality of the variables, either a Student’s t-test or a Wilcoxon test was used. Pearson correlation coefficients were calculated to evaluate the associations between methylation and anthropometric and biochemical parameters. Overall survival analyses were conducted using Kaplan–Meier curves, and multivariate proportional regression was used to calculate odds ratios (ORs) [95% confidence intervals (CIs)] and area under curve (AUC) for SFRP2 methylation adjusted by age, sex, BMI, HDL, triglycerides and cancer location. Logistic and linear regression analyses were conducted using SFRP2 promoter methylation in tumor, adjusted for age, sex and BMI."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}