FBW7 suppresses metastasis of colorectal cancer by inhibiting HIF1α/CEACAM5 functional axis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29910683", "kind": "science-record", "revision": 9, "content_hash": "sha256:24e1220782153b53435e608dff2d191aa86ffcc3397969462a92a561c7e4a620", "created_at": "2026-11-01T15:40:34Z", "updated_at": "2026-11-01T22:43:25Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "FBW7 suppresses metastasis of colorectal cancer by inhibiting HIF1α/CEACAM5 functional axis.", "doi": "10.7150/ijbs.24505", "pmid": "29910683", "authors": ["Qingguo Li", "Yaqi Li", "Jing Li", "Yanlei Ma", "Weixing Dai", "Shaobo Mo", "Ye Xu", "Xinxiang Li", "Sanjun Cai"], "journal": "International journal of biological sciences", "year": 2018, "abstract": "F-box and WD repeat domain-containing 7 (FBW7) functions as a major tumor suppressor by targeting oncoproteins for degradations. FBW7 has been reported to be one of the most frequently mutated genes in colorectal cancer (CRC). However, its roles and possible mechanisms in the development of CRC are still unclear. In the present study, we adopted immunohistochemistry staining in tissue microarray (TMA), consisting of 276 samples from stage I-IV CRC patients, and analyzed the correlation between FBW7 expression and clinicopathological parameters, as well as overall survival (OS) and disease-free survival (DFS). The impact of FBW7 on migration was further validated in vitro. Whole-genome expression microarray (GEO,accession numbers GSE76443), was then analyzed to find the possible target of FBW7. The results were verified by functional experiments in vitro and IHC staining of TMA. Finally, luciferase and chromatin immunoprecipitation (ChIP) assays were carried out to identify the possible mechanisms. The expression level of FBW7 in TMA was negatively correlated with serum CEA level, venous invasion, N stage and M stage, and positively associated with the survival of CRC patients(P<0.05). Ectopic FBW7 expression significantly suppressed migration of colon cancer cells in vitro. GEO analysis revealed that decreased FBW7 significantly correlated with increased level of CEACAM5, which encoded CEA. The correlation was verified by IHC of TMA and silencing CEACAM5 inhibited migration in vitro. Mechanistically, we demonstrated that CEACAM5 was a HIF1α target gene and that FBW7 regulated CEACAM5 in a HIF1α-dependent manner. In conclusion, our results revealed that FBW7 suppressed migration through regulation of the HIF1α/CEACAM5 axis in colorectal cancer. Therefore, our study sheds novel lights on the impact of FBW7 on HIF1α/CEACAM5 signaling axis and constitutes potential prognostic predictors and therapeutic targets for CRC.", "claims": [{"id": "claim-method", "statement": "The Student t test was used for statistical analysis unless otherwise noted, with P < 0.05 considered significant. In IHC assays of CRC samples, Spearman's Rank correlation assay was used to determine the correlation between FBW7 and clinicopathological factors. Survival analysis was performed using the Kaplan-Meier and log-rank method.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29910683", "locator": "sections[13] \"Statistical analysis\" paragraph 2", "quote": "The Student t test was used for statistical analysis unless otherwise noted, with P < 0.05 considered significant. In IHC assays of CRC samples, Spearman's Rank correlation assay was used to determine the correlation between FBW7 and clinicopathological factors. Survival analysis was performed using the Kaplan-Meier and log-rank method."}], "state": "complete"}, {"id": "claim-data-access", "statement": "To identify the possible molecular mechanism in colon cancer in response to FBW7 overexpression, we studied a whole-genome expression microarray (GEO: accession numbers GSE76443), and found decreased FBW7 expression significantly correlated with increased level of CEACAM5, which encoded CEA that was widely used clinically as both a blood and tissue tumor marker of epithelial malignancy, especially for CRC.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29910683", "locator": "sections[17] \"CEACAM5 is a target of FBW7 in colorectal cancer\" paragraph 2", "quote": "To identify the possible molecular mechanism in colon cancer in response to FBW7 overexpression, we studied a whole-genome expression microarray (GEO: accession numbers GSE76443), and found decreased FBW7 expression significantly correlated with increased level of CEACAM5, which encoded CEA that was widely used clinically as both a blood and tissue tumor marker of epithelial malignancy, especially for CRC."}], "state": "complete"}, {"id": "claim-target-result", "statement": "FBW7 suppresses colorectal cancer cell migration by regulating the HIF1α/CEACAM5 axis.", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "The analysis showed that the rate of 5-year OS was lower among the patients with FBW7-low tumors than among those with FBW7-high expression tumors (36.8% vs. 78.3%, χ2=47.415, P<0.001)."}, "evidence": [{"asset": "source:pmid:29910683", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In conclusion, our results revealed that FBW7 suppressed migration through regulation of the HIF1α/CEACAM5 axis in colorectal cancer."}, {"asset": "source:pmid:29910683", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Whole-genome expression microarray (GEO,accession numbers GSE76443), was then analyzed to find the possible target of FBW7."}, {"asset": "source:pmid:29910683", "locator": "sections[15] \"High FBW7 staining correlates with better survival outcomes of CRC\" paragraph 4", "quote": "To evaluate the association between FBW7 expression and survival outcomes among patients with CRC, we stratified the patients into FBW7-low and FBW7-high expression subgroups and then used Kaplan-Meier curves to compare the overall survival (OS) and disease-free survival (DFS) of the two subgroups (Fig.1c, d)."}, {"asset": "source:pmid:29910683", "locator": "sections[15] \"High FBW7 staining correlates with better survival outcomes of CRC\" paragraph 4", "quote": "The analysis showed that the rate of 5-year OS was lower among the patients with FBW7-low tumors than among those with FBW7-high expression tumors (36.8% vs. 78.3%, χ2=47.415, P<0.001)."}, {"asset": "source:pmid:29910683", "locator": "sections[15] \"High FBW7 staining correlates with better survival outcomes of CRC\" paragraph 4", "quote": "When analyzing the DFS, forty-two patients with distant metastases were excluded from the study, the results indicated that the 5-year DFS were 44.7% and 80.0% for those with low and high FBW7 expression (χ2=32.769, P<0.001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "FBW7 suppresses colorectal cancer cell migration by regulating the HIF1α/CEACAM5 axis.", "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:29910683"], "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:GSE76443"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:student_t", "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:GSE76443"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:student_t"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:29910683", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7150/ijbs.24505", "sha256": "sha256:f2f8dfd43d36f850e3fe33e62f89ecb6816a910232ec0ed5348a7e6692c712ac", "bytes": 22829, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7150/ijbs.24505", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6001674", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE76443", "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=GSE76443", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE76443", "version": null, "note": "To identify the possible molecular mechanism in colon cancer in response to FBW7 overexpression, we studied a whole-genome expression microarray (GEO: accession numbers GSE76443), and found decreased FBW7 expression significantly correlated with increased level of CEACAM5, which encoded CEA that was widely used clinically as both a blood and tissue tumor marker of epithelial malignancy, especially for CRC.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "To identify the possible molecular mechanism in colon cancer in response to FBW7 overexpression, we studied a whole-genome expression microarray (GEO: accession numbers GSE76443), and found decreased FBW7 expression significantly correlated with increased level of CEACAM5, which encoded CEA that was widely used clinically as both a blood and tissue tumor marker of epithelial malignancy, especially for CRC.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM2024737", "GSM2024738"], "sample_count": 2, "group_sizes": null, "group_sizes_basis": null, "platform": "17586", "taxon": "Homo sapiens", "title": "Gene expression data from SW1990 cells stably expressing Fbw7", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE76443 not downloaded", "asset:data:geo:GSE76443 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "The Student t test was used for statistical analysis unless otherwise noted, with P < 0.05 considered significant. In IHC assays of CRC samples, Spearman's Rank correlation assay was used to determine the correlation between FBW7 and clinicopathological factors. Survival analysis was performed using the Kaplan-Meier and log-rank method."}}, {"id": "method-2", "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-3", "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-4", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Spearman's Rank correlation"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "logrank_test", "expected_value": 0.001, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": ["method.student_t"]}, "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": false, "required_operations": [], "missing_operations": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "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": ["GSE76443"], "resolved_accessions": ["GSE76443"], "statements": ["To identify the possible molecular mechanism in colon cancer in response to FBW7 overexpression, we studied a whole-genome expression microarray (GEO: accession numbers GSE76443), and found decreased FBW7 expression significantly correlated with increased level of CEACAM5, which encoded CEA that was widely used clinically as both a blood and tissue tumor marker of epithelial malignancy, especially for CRC."], "basis": "The paper names GSE76443 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": [], "assets": ["source:pmid:29910683", "data:geo:GSE76443"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "student_t", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE76443"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:34:48Z", "independence": "same_provider"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 8, "usage": {"prompt_tokens": 49881, "completion_tokens": 3886, "cached_tokens": 7712}}, "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:29910683", "type": "paper", "label": "pmid:29910683"}, {"id": "source:pmid:29910683", "type": "manuscript", "label": "PMID 29910683 full text"}, {"id": "data:geo:GSE76443", "type": "dataset", "label": "GEO GSE76443"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:29910683", "type": "paper", "label": "pmid:29910683"}, {"id": "source:pmid:29910683", "type": "manuscript", "label": "PMID 29910683 full text"}, {"id": "data:geo:GSE76443", "type": "dataset", "label": "GEO GSE76443"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-29910683", "type": "extraction", "used": ["source:pmid:29910683"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE76443", "type": "accession_resolution", "used": ["data:geo:GSE76443"], "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:29910683", "parent_hash": "sha256:0e7dab9ee67410e463bf443ae94d82464ecb1d89711d94263d2e519382ee47ff", "fork_of": null, "generation": 8}, "gaps": ["asset:data:geo:GSE76443 licence not read", "asset:data:geo:GSE76443 not downloaded", "execution.not_run", "method.student_t", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:student_t"], "assays": [{"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": ["ll unclear. In the present study, we adopted immunohistochemistry staining in tissue microarray (TMA), consist", "ified by functional experiments in vitro and IHC staining of TMA. Finally, luciferase and chr", "encoded CEA. The correlation was verified by IHC of TMA and silencing CEACAM5 inhibited migra", "ed, with P < 0.05 considered significant. In IHC assays of CRC samples, Spearman's Rank corre"], "order_basis": "paper_text_order:396", "id": "assay:1"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["pted immunohistochemistry staining in tissue microarray (TMA), consisting of 276 samples from stage", "validated in vitro. Whole-genome expression microarray (GEO,accession numbers GSE76443), was then a"], "order_basis": "paper_text_order:436", "id": "assay:2"}, {"role": "data_generation", "definition_id": "clinical_cohort", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["thods Patient specimens and TMA construction We recruited 276 formalin-fixed, paraffin-embedded CRC ti"], "order_basis": "paper_text_order:2044", "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": ["n (ATCC) (Manassas, VA, USA). The cells were cultured in medium according to The Defense Technical in"], "order_basis": "paper_text_order:2855", "id": "assay:4"}, {"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": ["The Student t test was used for statistical analysis unless otherwise noted, with P < 0.05 considered significant. In IHC assays of CRC samples, Spearman's Rank correlation assay was used to determine the correlation between FBW7 and clinicopathological factors. Survival analysis was performed using the Kaplan-Meier and log-rank method."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}