Construction of a DDR-related signature for predicting of prognosis in metastatic colorectal carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36816926", "kind": "science-record", "revision": 3, "content_hash": "sha256:5843aff44f86b3ff0643f72434503b98168c9caa87442404511a0a0862c6aa63", "created_at": "2026-11-01T19:01:24Z", "updated_at": "2026-11-01T22:08:50Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Construction of a DDR-related signature for predicting of prognosis in metastatic colorectal carcinoma.", "doi": "10.3389/fonc.2023.1043160", "pmid": "36816926", "authors": ["Maohua Wei", "Junyan Su", "Jiali Zhang", "Siyao Liu", "Jia Ma", "Xiang Peng Meng"], "journal": "Frontiers in oncology", "year": 2023, "abstract": "Background: Colorectal cancer (CRC) is the third most prevalent malignancy and the one of most lethal cancer. Metastatic CRC (mCRC) is the third most common cause of cancer deaths worldwide. DNA damage response (DDR) genes are closely associated with the tumorigenesis and development of CRC. In this study, we aimed to construct a DDR-related gene signature for predicting the prognosis of mCRC patients.\nMethods: The gene expression and corresponding clinical information data of CRC/mCRC patients were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. A prognostic model was obtained and termed DDRScore by the multivariate Cox proportional hazards regression in the patients with mCRC. The Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) curves were employed to validate the predictive ability of the prognostic model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed for patients between the high-DDRscore and low-DDRscore groups.\nResults: We constructed a prognostic model consisting of four DDR-related genes (EME2, MSH4, MLH3, and SPO11). Survival analysis showed that patients in the high-DDRscore group had a significantly worse OS than those in the low-DDRscore group. The area under the curve (AUC) value of the ROC curve of the predictive model is 0.763 in the training cohort GSE72970, 0.659 in the stage III/IV colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA) data portal, and 0.639 in another validation cohort GSE39582, respectively. GSEA functional analysis revealed that the most significantly enriched pathways focused on nucleotide excision repair, base excision repair, homologous recombination, cytokine receptor interaction, chemokine signal pathway, cell adhesion molecules cams, ECM-receptor interaction, and focal adhesion.\nConclusion: The DDRscore was identified as an independent prognostic and therapy response predictor, and the DDR-related genes may be potential diagnosis or prognosis biomarkers for mCRC patients.", "claims": [{"id": "claim-method", "statement": "A prognostic model was obtained and termed DDRScore by the multivariate Cox proportional hazards regression in the patients with mCRC.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36816926", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "A prognostic model was obtained and termed DDRScore by the multivariate Cox proportional hazards regression in the patients with mCRC."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: The datasets of CRC were collected from the Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) and TCGA-COAD (https://xenabrowser.net/datapages).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36816926", "locator": "sections[19] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: The datasets of CRC were collected from the Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) and TCGA-COAD (https://xenabrowser.net/datapages)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A prognostic model was obtained and termed DDRScore by the multivariate Cox proportional hazards regression in the patients with mCRC.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36816926", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "A prognostic model was obtained and termed DDRScore by the multivariate Cox proportional hazards regression in the patients with mCRC."}, {"asset": "source:pmid:36816926", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The gene expression and corresponding clinical information data of CRC/mCRC patients were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases."}, {"asset": "source:pmid:36816926", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We constructed a prognostic model consisting of four DDR-related genes (EME2, MSH4, MLH3, and SPO11)."}, {"asset": "source:pmid:36816926", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The area under the curve (AUC) value of the ROC curve of the predictive model is 0.763 in the training cohort GSE72970, 0.659 in the stage III/IV colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA) data portal, and 0.639 in another validation cohort GSE39582, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A prognostic model was obtained and termed DDRScore by the multivariate Cox proportional hazards regression in the patients with mCRC.", "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:36816926"], "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:GSE39582"], "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:GSE39582"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36816926", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2023.1043160", "sha256": "sha256:935a606e614095cb4711b9ad51612194ab1840a1345fd510e5cb86c52d1f4321", "bytes": 49398, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2023.1043160", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9931195", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE39582", "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=GSE39582", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE39582", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: The datasets of CRC were collected from the Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) and TCGA-COAD (https://xenabrowser.net/datapages).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. 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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}}, {"id": "data:geo:GSE72970", "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=GSE72970", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE72970", "version": null, "note": "Publicly available datasets were analyzed in this study. 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