Lower Expression of CFTR Is Associated with Higher Mortality in a Meta-Analysis of Individuals with Colorectal Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36765944", "kind": "science-record", "revision": 4, "content_hash": "sha256:18e292958d67a4f3aea9abb93a2f601f04e8725f47e1c68b04c6ebe2416b4e09", "created_at": "2026-11-01T19:01:21Z", "updated_at": "2026-11-01T22:51:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Lower Expression of CFTR Is Associated with Higher Mortality in a Meta-Analysis of Individuals with Colorectal Cancer.", "doi": "10.3390/cancers15030989", "pmid": "36765944", "authors": ["Patricia Scott", "Shuo Wang", "Guillaume Onyeaghala", "Nathan Pankratz", "Timothy Starr", "Anna E Prizment"], "journal": "Cancers", "year": 2023, "abstract": "Individuals with cystic fibrosis (CF), caused by biallelic germline mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), have higher risk and earlier onset of colorectal cancer (CRC). A subset of CRC patients in the non-CF population expresses low levels of tumoral CFTR mRNA which may also cause decreased CFTR activity. To determine the consequences of reduced CFTR expression in this population, we investigated association of tumoral CFTR expression with overall and disease-specific mortality in CRC patients. CFTR mRNA expression, clinical factors and survival data from 1177 CRC patients reported in the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus studies GSE39582 and GSE17538 were included. Log-transformed and z-normalized [mean = 0, standard deviation (SD) = 1] CFTR expression values were modeled as quartiles or dichotomized at the median. Univariate and multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for overall and disease-specific mortality in individual studies and meta-analyses. Analyses of each of the three individual datasets showed a robust association of decreased CFTR expression with increased mortality. In meta-analyses adjusted for stage at diagnosis, age and sex, CFTR expression was inversely associated with risk of overall death [pooled HR (95% CI): 0.70 (0.57-0.86)] and disease-specific death [pooled HR (95% CI): 0.68 (0.47-0.99)]. Associations did not differ by stage at diagnosis, age, or sex. Meta-analysis of overall death stratified by microsatellite instable (MSI) versus microsatellite stable (MSS) status indicated potential interaction between MSI/MSS status and CFTR expression, (p-interaction: 0.06). The findings from these three datasets support the hypothesis that low CFTR expression is associated with increased CRC mortality.", "claims": [{"id": "claim-method", "statement": "To estimate the risk of overall and disease-specific death across CFTR expression categories, we used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36765944", "locator": "sections[8] \"2.4. Statistical Analysis\" paragraph 3", "quote": "To estimate the risk of overall and disease-specific death across CFTR expression categories, we used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All datasets analyzed in this study are publicly available. These data can be found at http://www.cbioportal.org/: data folder “Coadread_tcga_pan_can_atlas_2018; and NCBI GEO databases GSE17538 and GSE39582” (accessed on 27 September 2020, 20 June 2021 and 20 June 2021 respectively).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36765944", "locator": "sections[20] \"Data Availability Statement\" paragraph 2", "quote": "All datasets analyzed in this study are publicly available. These data can be found at http://www.cbioportal.org/: data folder “Coadread_tcga_pan_can_atlas_2018; and NCBI GEO databases GSE17538 and GSE39582” (accessed on 27 September 2020, 20 June 2021 and 20 June 2021 respectively)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In meta-analyses adjusted for stage at diagnosis, age and sex, CFTR expression was inversely associated with risk of overall death [pooled HR (95% CI): 0.70 (0.57–0.86)] and disease-specific death [pooled HR (95% CI): 0.68 (0.47–0.99)].", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "In meta-analyses adjusted for stage at diagnosis, age and sex, CFTR expression was inversely associated with risk of overall death [pooled HR (95% CI): 0.70 (0.57–0.86)] and disease-specific death [pooled HR (95% CI): 0.68 (0.47–0.99)]."}, "evidence": [{"asset": "source:pmid:36765944", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "In meta-analyses adjusted for stage at diagnosis, age and sex, CFTR expression was inversely associated with risk of overall death [pooled HR (95% CI): 0.70 (0.57–0.86)] and disease-specific death [pooled HR (95% CI): 0.68 (0.47–0.99)]."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In meta-analyses adjusted for stage at diagnosis, age and sex, CFTR expression was inversely associated with risk of overall death [pooled HR (95% CI): 0.70 (0.57–0.86)] and disease-specific death [pooled HR (95% CI): 0.68 (0.47–0.99)].", "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:36765944"], "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:GSE17538"], "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:GSE17538"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36765944", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/cancers15030989", "sha256": "sha256:3c0de3620726075eeb3a7c73b733116052748e710cc104da3a74f9527c01cfbe", "bytes": 47548, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/cancers15030989", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9913301", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE17538", "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=GSE17538", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE17538", "version": null, "note": "All datasets analyzed in this study are publicly available. These data can be found at http://www.cbioportal.org/: data folder “Coadread_tcga_pan_can_atlas_2018; and NCBI GEO databases GSE17538 and GSE39582” (accessed on 27 September 2020, 20 June 2021 and 20 June 2021 respectively).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All datasets analyzed in this study are publicly available. 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"platform": "570", "taxon": "Homo sapiens", "title": "Gene expression Classification of Colon Cancer defines six molecular subtypes with distinct clinical, molecular and survival characteristics [Expression]", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE17538 not downloaded", "asset:data:geo:GSE17538 licence not read", "asset:data:geo:GSE39582 not downloaded", "asset:data:geo:GSE39582 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "To estimate the risk of overall and disease-specific death across CFTR expression categories, we used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs)."}}, {"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": "meta_analysis", "specific": "fixed_effects", "label": "Meta-analysis / evidence synthesis", "dsl_operations": [], "missing_operations": ["fixed_effects_pool"], "expressible": false, "parameters": {"i_squared": "ection and p-values for heterogeneity between studies were no"}, "data_shapes": ["study_level_effect_estimates"], "evidence": {"score": 0.8, "band": "high", "quote": "fixed-effect"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "cox_ph", "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", "GSE17538"], "resolved_accessions": ["GSE39582", "GSE17538"], "statements": ["All datasets analyzed in this study are publicly available. These data can be found at http://www.cbioportal.org/: data folder “Coadread_tcga_pan_can_atlas_2018; and NCBI GEO databases GSE17538 and GSE39582” (accessed on 27 September 2020, 20 June 2021 and 20 June 2021 respectively)."], "basis": "The paper names GSE39582, GSE17538 in NCBI GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:36765944", "data:geo:GSE17538"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE17538"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:26:46Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14007, "completion_tokens": 1755, "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:36765944", "type": "paper", "label": "pmid:36765944"}, {"id": "source:pmid:36765944", "type": "manuscript", "label": "PMID 36765944 full text"}, {"id": "data:geo:GSE17538", "type": "dataset", "label": "GEO GSE17538"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36765944", "type": "paper", "label": "pmid:36765944"}, {"id": "source:pmid:36765944", "type": "manuscript", "label": "PMID 36765944 full text"}, {"id": "data:geo:GSE17538", "type": "dataset", "label": "GEO GSE17538"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36765944", "type": "extraction", "used": ["source:pmid:36765944"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE17538", "type": "accession_resolution", "used": ["data:geo:GSE17538"], "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:36765944", "parent_hash": "sha256:43580523ed11aaad1cfc107c1f93eaba5e947f26f6b0cc35e0dc4e57aa3484ef", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE17538 licence not read", "asset:data:geo:GSE17538 not downloaded", "asset:data:geo:GSE39582 licence not read", "asset:data:geo:GSE39582 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["To estimate the risk of overall and disease-specific death across CFTR expression categories, we used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs)."], "order_basis": "analysis_only", "id": "assay:1"}]}