Prognostic Analysis of Differentially Expressed DNA Damage Repair Genes in Bladder Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35685866", "kind": "science-record", "revision": 4, "content_hash": "sha256:5d6ce352c156625f79bad3bcf3525586fdfa7632e25f5607f8758276173f3f52", "created_at": "2026-11-01T18:14:38Z", "updated_at": "2026-11-01T22:06:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prognostic Analysis of Differentially Expressed DNA Damage Repair Genes in Bladder Cancer.", "doi": "10.3389/pore.2022.1610267", "pmid": "35685866", "authors": ["Yong Yang", "Jieqing Yu", "Yuanping Xiong", "Jiansheng Xiao", "Daofeng Dai", "Feng Zhang"], "journal": "Pathology oncology research : POR", "year": 2022, "abstract": "Bladder cancer (BCa) is the tenth most common tumor in humans. DNA damage repair genes (DDRGs) play important roles in many malignant tumors; thus, their functions in BCa should also be explored. We performed a comprehensive analysis of the expression profiles of DDRGs in 410 BCa tumors and 19 normal tissues from The Cancer Genome Atlas database. We identified 123 DDRGs differentially expressed between BCa tumors and normal tissues, including 95 upregulated and 28 downregulated genes. We detected 22 DDRGs associated with overall survival (OS) of patients with BCa by performing univariate Cox regression analysis. To explore the interactions between OS-associated DDRGs, we constructed a PPI network, which showed that the top six DDRGs (CDCA2, FOXM1, PBK, RRM2, ORC1, and HDAC4) with the highest scores in the PPI network might play significant roles in OS of BCa. Moreover, to investigate the latent regulatory mechanism of these OS-associated DDRGs, we analyzed the transcription factors (TFs)-DDRGs regulatory network. The core seven TFs (NCAPG, DNMT1, LMNB1, BRCA1, E2H2, CENPA, and E2F7) were shown to be critical regulators of the OS-related DDRGs. The 22 DDRGs were incorporated into a stepwise multivariable Cox analysis. Then, we built the index of risk score based on the expression of 8 DDRGs (CAD, HDAC10, JDP2, LDLR, PDGFRA, POLA2, SREBF1, and STAT1). The p-value < 0.0001 in the Kaplan-Meier survival plot and an area under the ROC curve (AUC) of 0.771 in TCGA-BLCA training dataset suggested the high specificity and sensitivity of the prognostic index. Furthermore, we validated the risk score in the internal TCGA-BLCA and an independent GSE32894 dataset, with AUC of 0.743 and 0.827, respectively. More importantly, the multivariate Cox regression and stratification analysis demonstrated that the predictor was independent of various clinical parameters, including age, tumor stage, grade, and number of positive tumor lymph nodes. In summary, a panel of 8 DNA damage repair genes associated with overall survival in bladder cancer may be a useful prognostic tool.", "claims": [{"id": "claim-method", "statement": "These survival-related DDRGs were integrated into a stepwise multivariate Cox regression to select the optimal model for prognosis [14].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35685866", "locator": "sections[8] \"Univariate and Multivariate Cox Regression Analysis\" paragraph 2", "quote": "These survival-related DDRGs were integrated into a stepwise multivariate Cox regression to select the optimal model for prognosis [14]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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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 eight-gene DNA damage repair prognostic index was validated in the internal TCGA-BLCA and independent GSE32894 datasets, with AUCs of 0.743 and 0.827, respectively.", "kind": "quantitative", "target": {"value": 0.743, "unit": "auc", "tolerance": null, "source": "Furthermore, we validated the risk score in the internal TCGA-BLCA and an independent GSE32894 dataset, with AUC of 0.743 and 0.827, respectively."}, "evidence": [{"asset": "source:pmid:35685866", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Furthermore, we validated the risk score in the internal TCGA-BLCA and an independent GSE32894 dataset, with AUC of 0.743 and 0.827, respectively."}, {"asset": "source:pmid:35685866", "locator": "sections[16] \"Development and Validation of the DNA Damage Repair Prognostic Index\" paragraph 2", "quote": "The prognostic index was confirmed in TCGA-BLCA internal validation dataset, with a similar KM plot (p-value <0.0001) and ROC curve (AUC = 0.743, p = 3.77E-06) (Figure 4B)."}, {"asset": "source:pmid:35685866", "locator": "sections[16] \"Development and Validation of the DNA Damage Repair Prognostic Index\" paragraph 5", "quote": "A significant p-value < 0.0001 in the KM survival analysis and an area under the ROC curve of 0.827 verified the efficiency of our prognostic model, p = 2.29E-07 (Figure 4C)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The eight-gene DNA damage repair prognostic index was validated in the internal TCGA-BLCA and independent GSE32894 datasets, with AUCs of 0.743 and 0.827, respectively.", "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:35685866"], "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. 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