Dysregulated Forkhead Box (FOX) Genes Association with Survival Prognosis, Anti-tumor Immunity, and Key Targeting Drugs in Colon Adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38310407", "kind": "science-record", "revision": 4, "content_hash": "sha256:5888f15048919b51292d428f66fbcf7b6031ed08756b6a6a83bb5fdaa4aa4413", "created_at": "2026-11-01T19:20:15Z", "updated_at": "2026-11-01T22:53:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Dysregulated Forkhead Box (FOX) Genes Association with Survival Prognosis, Anti-tumor Immunity, and Key Targeting Drugs in Colon Adenocarcinoma.", "doi": "10.34172/aim.2023.77", "pmid": "38310407", "authors": ["Qian Xie", "Jie Wang", "Xingchen Peng"], "journal": "Archives of Iranian medicine", "year": 2023, "abstract": "BACKGROUND: Several studies have revealed that the aberrant expressions of forkhead box (FOX) genes are associated with carcinogenesis. However, the crucial biological functions of the FOX gene in colon adenocarcinoma (COAD) remain unknown.\nMETHODS: The TCGA-COAD dataset (n=328) was utilized for determining the deregulated FOX genes and their association with functional enrichment, protein-protein interaction (PPI), survival prognosis, anti-tumor immunity, cancer-associated pathways, and biological processes in COAD. In addition, we used GSE166427 (GPL13667) as a validation cohort (n=196). Molecular docking studies were applied to perform the drug interactions.\nRESULTS: The FOX genes are deregulated in the COAD (Log2 FC>0.50, P<0.05), and the PPI network of FOX members is substantially related to the enrichment of cancerous signaling, immune responses, and cellular development (FDR<0.05). A worse prognosis for overall survival in COAD individuals is connected with the subgroup of FOX transcripts (P≤0.05). FOXD4, FOXH1, and FOXS1 were identified as predictive variables in the univariate and multivariate Cox regression models (P≤0.05). FOXH1 and FOXS1 are substantially linked to the deregulated immunity in COAD (R>0.20, P<0.01). Furthermore, FOXS1 expression regulates cancer-associated pathways and biological processes (P<0.05). Moreover, FOXD4, FOXH1, and FOXS1 are genetically altered and showed diagnostic efficacy in COAD. We revealed that FOXD4, FOXH1, and FOXS1 are consistently deregulated in GSE166427 (P<0.05). Finally, molecular docking revealed that FOXH1 interacted with various drugs, including belinostat, entinostat, and panobinostat.\nCONCLUSION: The FOX genes have a strong correlation with the poor prognosis for survival, tumor immunity, cancer-associated pathways, and biochemical processes that cause the pathogenesis of COAD.", "claims": [{"id": "claim-method", "statement": "The survival disparities between the high-expression group (HEG) and low-expression group (LEG) of FOX genes in COAD individuals were identified using the Kaplan-Meier method (HEG > median > LEG). Utilizing the R package “survival”, the survival implications of significant FOX genes in the TCGA COAD database were investigated.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38310407", "locator": "sections[7] \"Survival Analysis of FOX Genes in COAD\" paragraph 2", "quote": "The survival disparities between the high-expression group (HEG) and low-expression group (LEG) of FOX genes in COAD individuals were identified using the Kaplan-Meier method (HEG > median > LEG). Utilizing the R package “survival”, the survival implications of significant FOX genes in the TCGA COAD database were investigated."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data Availability Statement The TCGA-COAD cohort is downloaded from The Cancer Genome Atlas (TCGA) database (https://portal.gdc.cancer.gov/). The mutation and CNA data (n = 220) were used from the cBioPortal (http://www.cbioportal.org/). The GEO data (GSE166427) was downloaded from the national center for biotechnology information (https://www.ncbi.nlm.nih.gov/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38310407", "locator": "sections[27] \"fn-group\" paragraph 1", "quote": "Data Availability Statement The TCGA-COAD cohort is downloaded from The Cancer Genome Atlas (TCGA) database (https://portal.gdc.cancer.gov/). The mutation and CNA data (n = 220) were used from the cBioPortal (http://www.cbioportal.org/). The GEO data (GSE166427) was downloaded from the national center for biotechnology information (https://www.ncbi.nlm.nih.gov/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "FOXD4, FOXH1, and FOXS1 were identified as predictive variables in the univariate and multivariate Cox regression models (P≤0.05).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38310407", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "FOXD4, FOXH1, and FOXS1 were identified as predictive variables in the univariate and multivariate Cox regression models (P≤0.05)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "FOXD4, FOXH1, and FOXS1 were identified as predictive variables in the univariate and multivariate Cox regression models (P≤0.05).", "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:38310407"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38310407", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.34172/aim.2023.77", "sha256": "sha256:fda47bdc90879a648f2a1683894c8199a6f7846c5818be61641c2c8078a98f21", "bytes": 46492, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.34172/aim.2023.77", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10862056", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "The survival disparities between the high-expression group (HEG) and low-expression group (LEG) of FOX genes in COAD individuals were identified using the Kaplan-Meier method (HEG > median > LEG). Utilizing the R package “survival”, the survival implications of significant FOX genes in the TCGA COAD database were investigated."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-3", "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": 0.7, "band": "medium", "quote": "Cox regression"}}, {"id": "method-4", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}], "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "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": "R4", "reachable": false, "accessions": ["GSE166427 (GPL13667)"], "resolved_accessions": [], "statements": ["Data Availability Statement The TCGA-COAD cohort is downloaded from The Cancer Genome Atlas (TCGA) database (https://portal.gdc.cancer.gov/). The mutation and CNA data (n = 220) were used from the cBioPortal (http://www.cbioportal.org/). The GEO data (GSE166427) was downloaded from the national center for biotechnology information (https://www.ncbi.nlm.nih.gov/)."], "basis": "The paper names GSE166427 (GPL13667), but the accession does not resolve in the repository (no reason recorded), so the data cannot be reached from here. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["survival_km"], "assets": ["source:pmid:38310407"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "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": "2026-11-01T19:07:28Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13080, "completion_tokens": 2044, "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:38310407", "type": "paper", "label": "pmid:38310407"}, {"id": "source:pmid:38310407", "type": "manuscript", "label": "PMID 38310407 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38310407", "type": "paper", "label": "pmid:38310407"}, {"id": "source:pmid:38310407", "type": "manuscript", "label": "PMID 38310407 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38310407", "type": "extraction", "used": ["source:pmid:38310407"], "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:38310407", "parent_hash": "sha256:fc55240b19c34cd324157cccde3931523fa79ddacb8dce0718ead0fbfabacd87", "fork_of": null, "generation": 3}, "gaps": ["execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The survival disparities between the high-expression group (HEG) and low-expression group (LEG) of FOX genes in COAD individuals were identified using the Kaplan-Meier method (HEG > median > LEG). 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