Identification of key claudin genes associated with survival prognosis and diagnosis in colon cancer through integrated bioinformatic analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37799140", "kind": "science-record", "revision": 4, "content_hash": "sha256:05bc76ddc911d97a1d70fb471049ed24078a051ee8cf1ebd2c862a29b32842e0", "created_at": "2026-11-01T19:02:39Z", "updated_at": "2026-11-01T22:52:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of key claudin genes associated with survival prognosis and diagnosis in colon cancer through integrated bioinformatic analysis.", "doi": "10.3389/fgene.2023.1221815", "pmid": "37799140", "authors": ["Rana A Alghamdi", "Maryam H Al-Zahrani"], "journal": "Frontiers in genetics", "year": 2023, "abstract": "The claudin multigene family is associated with various aberrant physiological and cellular signaling pathways. However, the association of claudins with survival prognosis, signaling pathways, and diagnostic efficacy in colon cancer remains poorly understood. Methods: Through the effective utilization of various bioinformatics methods, including differential gene expression analysis, gene set enrichment analysis protein-protein interaction (PPI) network analysis, survival analysis, single sample gene set enrichment analysis (ssGSEA), mutational variance analysis, and identifying receiver operating characteristic curve of claudins in The Cancer Genome Atlas colon adenocarcinoma (COAD). Results: We found that: CLDN2, CLDN1, CLDN14, CLDN16, CLDN18, CLDN9, CLDN12, and CLDN6 are elevated in COAD. In contrast, the CLDN8, CLDN23, CLDN5, CLDN11, CLDN7, and CLDN15 are downregulated in COAD. By analyzing the public datasets GSE15781 and GSE50760 from NCBI-GEO (https://www.ncbi.nlm.nih.gov/geo/), we have confirmed that CLDN1, CLDN2, and CLDN14 are significantly upregulated and CLDN8 and CLDN23 are significantly downregulated in normal colon, colon adenocarcinoma tumor, and liver metastasis of colon adenocarcinoma tissues from human samples. Various claudins are mutated and found to be associated with diagnostic efficacy in COAD. Conclusion: The claudin gene family is associated with prognosis, immune regulation, signaling pathway regulations, and diagnosis of COAD. These findings may provide new molecular insight into claudins in the treatment of colon cancer.", "claims": [{"id": "claim-method", "statement": "To assess diagnostic values of the prognostic genes, the receiver operating characteristic (ROC) curve was plotted and the area under the ROC curve (AUC) was calculated using the “pROC” R package (Robin et al., 2011) to evaluate the capability of distinguishing COAD and normal samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37799140", "locator": "sections[11] \"2.8 Diagnostic efficacy evaluation of differentially expressed claudins in the COAD\" paragraph 2", "quote": "To assess diagnostic values of the prognostic genes, the receiver operating characteristic (ROC) curve was plotted and the area under the ROC curve (AUC) was calculated using the “pROC” R package (Robin et al., 2011) to evaluate the capability of distinguishing COAD and normal samples."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37799140", "locator": "sections[27] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The expression levels of CLDN2, CLDN1, CLDN14, CLDN16, CLDN12, CLDN8, CLDN23, CLDN5, CLDN11, and CLDN7 showed strong diagnostic value for colon cancer patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37799140", "locator": "sections[22] \"3.9 Claudins exhibited the diagnostic efficacy in colon cancers\" paragraph 2", "quote": "We found that the AUC value of CLDN2, CLDN1, CLDN14, CLDN16, CLDN12, CLDN8, CLDN23, CLDN5, CLDN11, and CLDN7 is above 0.80, indicating that these claudins have strong diagnostic value for colon cancer patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The expression levels of CLDN2, CLDN1, CLDN14, CLDN16, CLDN12, CLDN8, CLDN23, CLDN5, CLDN11, and CLDN7 showed strong diagnostic value for colon cancer patients.", "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:37799140"], "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:GSE15781"], "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:GSE15781"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37799140", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2023.1221815", "sha256": "sha256:907bd96af177bd7c324339767f880e28f65ceee56f27d26cc410ab57ec4e2d25", "bytes": 67017, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2023.1221815", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10550083", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE15781", "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=GSE15781", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE15781", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM396309", "GSM396310", "GSM396311", "GSM396312", "GSM396313", "GSM396314", "GSM396315", "GSM396316", "GSM396317", "GSM396318", "GSM396319", "GSM396320", "GSM396321", "GSM396322", "GSM396323", "GSM396324", "GSM396325", "GSM396326", "GSM396327", "GSM396328", "GSM396329", "GSM396330", "GSM396331", "GSM396332", "GSM396333", "GSM396334", "GSM396335", "GSM396336", "GSM396337", "GSM396338", "GSM396339", "GSM396340", "GSM396341", "GSM396342", "GSM396343", "GSM396344", "GSM396345", "GSM396346", "GSM396347", "GSM396348", "GSM396349", "GSM396350"], "sample_count": 42, "group_sizes": null, "group_sizes_basis": null, "platform": "2986", "taxon": "Homo sapiens", "title": "New specific molecular targets for radiochemotherapy in colorectal cancer", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE50760", "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=GSE50760", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE50760", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1228184", "GSM1228185", "GSM1228186", "GSM1228187", "GSM1228188", "GSM1228189", "GSM1228190", "GSM1228191", "GSM1228192", "GSM1228193", "GSM1228194", "GSM1228195", "GSM1228196", "GSM1228197", "GSM1228198", "GSM1228199", "GSM1228200", "GSM1228201", "GSM1228202", "GSM1228203", "GSM1228204", "GSM1228205", "GSM1228206", "GSM1228207", "GSM1228208", "GSM1228209", "GSM1228210", "GSM1228211", "GSM1228212", "GSM1228213", "GSM1228214", "GSM1228215", "GSM1228216", "GSM1228217", "GSM1228218", "GSM1228219", "GSM1228220", "GSM1228221", "GSM1228222", "GSM1228223", "GSM1228224", "GSM1228225", "GSM1228226", "GSM1228227", "GSM1228228", "GSM1228229", "GSM1228230", "GSM1228231", "GSM1228232", "GSM1228233", "GSM1228234", "GSM1228235", "GSM1228236", "GSM1228237"], "sample_count": 54, "group_sizes": null, "group_sizes_basis": null, "platform": "11154", "taxon": "Homo sapiens", "title": "Gene expression profiling study by RNA-seq in colorectal cancer", "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:GSE15781 not downloaded", "asset:data:geo:GSE15781 licence not read", "asset:data:geo:GSE50760 not downloaded", "asset:data:geo:GSE50760 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "To assess diagnostic values of the prognostic genes, the receiver operating characteristic (ROC) curve was plotted and the area under the ROC curve (AUC) was calculated using the “pROC” R package (Robin et al., 2011) to evaluate the capability of distinguishing COAD and normal samples."}}, {"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": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {"p_value": "roups, a Cox regression p-value of 0"}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Cox regression"}}, {"id": "method-4", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {"p_value": "In the Log-rank test, a p-value <0"}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Log-rank"}}, {"id": "method-5", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {"p_value": "between the two genes (p-value ≤0"}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson correlation"}}, {"id": "method-6", "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": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: roc."}, "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": ["GSE15781", "GSE50760"], "resolved_accessions": ["GSE15781", "GSE50760"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."], "basis": "The paper names GSE15781, GSE50760 in NCBI-GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "assets": ["source:pmid:37799140", "data:geo:GSE15781"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE15781"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:55:16Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 18948, "completion_tokens": 1739, "cached_tokens": 128}}, "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:37799140", "type": "paper", "label": "pmid:37799140"}, {"id": "source:pmid:37799140", "type": "manuscript", "label": "PMID 37799140 full text"}, {"id": "data:geo:GSE15781", "type": "dataset", "label": "GEO GSE15781"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37799140", "type": "paper", "label": "pmid:37799140"}, {"id": "source:pmid:37799140", "type": "manuscript", "label": "PMID 37799140 full text"}, {"id": "data:geo:GSE15781", "type": "dataset", "label": "GEO GSE15781"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37799140", "type": "extraction", "used": ["source:pmid:37799140"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE15781", "type": "accession_resolution", "used": ["data:geo:GSE15781"], "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:37799140", "parent_hash": "sha256:9c467c1a55091cf55c1d21040e4933b091b31dd9642ca8ef8842658e37a7a19b", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE15781 licence not read", "asset:data:geo:GSE15781 not downloaded", "asset:data:geo:GSE50760 licence not read", "asset:data:geo:GSE50760 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["GSEA score of angiogenesis, apical junction, apoptosis, epithelial-mesenchymal transition (EMT), hy"], "order_basis": "paper_text_order:4109", "id": "assay:1"}, {"role": "analysis", "definition_id": "diagnostic_evaluation", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["To assess diagnostic values of the prognostic genes, the receiver operating characteristic (ROC) curve was plotted and the area under the ROC curve (AUC) was calculated using the “pROC” R package (Robin et al., 2011) to evaluate the capability of distinguishing COAD and normal samples."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}