Identification of a DNA Damage Response and Repair-Related Gene-Pair Signature for Prognosis Stratification Analysis in Hepatocellular Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35496321", "kind": "science-record", "revision": 3, "content_hash": "sha256:6c4c77684e05463c7d76a14ce758b613cc366a7b86570abf53a981d0bf78655d", "created_at": "2026-11-01T18:14:22Z", "updated_at": "2026-11-01T21:27:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of a DNA Damage Response and Repair-Related Gene-Pair Signature for Prognosis Stratification Analysis in Hepatocellular Carcinoma.", "doi": "10.3389/fphar.2022.857060", "pmid": "35496321", "authors": ["Yi Chen", "Mengjia Huang", "Junkai Zhu", "Li Xu", "Wenxuan Cheng", "Xiaofan Lu", "Fangrong Yan"], "journal": "Frontiers in pharmacology", "year": 2022, "abstract": "Background: Nowadays, although the cause of hepatocellular carcinoma (HCC) mortality and recurrence remains at a high level, the 5-year survival rate is still very low. The DNA damage response and repair (DDR) pathway may affect HCC patients' survival by influencing tumor development and therapeutic response. It is necessary to identify a prognostic DDR-related gene signature to predict the outcome of patients. Methods: Level 3 mRNA expression and clinical information were extracted from the TCGA website. The GSE14520 datasets, ICGC-LIRI datasets, and a Chinese HCC cohort were served as validation sets. Univariate Cox regression analysis and LASSO-penalized Cox regression analysis were performed to construct the DDR-related gene pair (DRGP) signature. Kaplan-Meier survival curves and time-dependent receiver operating characteristic (ROC) analysis curves were calculated to determine the predictive ability of this prognostic model. Then, a prognostic nomogram was established to help clinical management. We investigated the difference in biological processes between HRisk and LRisk by conducting several enrichment analyses. The TIDE algorithm and R package \"pRRophetic\" were applied to estimate the immunotherapeutic and chemotherapeutic response. Results: We constructed the prognostic signature based on 23 DDR-related gene pairs. The patients in the training datasets were divided into HRisk and LRisk groups at median cut-off. The HRisk group had significantly poorer OS than the LRisk group, and the signature was an independent prognostic indicator in HCC. Furthermore, a nomogram of the riskscore combined with TNM stage was constructed and detected by the calibration curve and decision curve. The LRisk group was associated with higher expression of HBV oncoproteins and metabolism pathways, while DDR-relevant pathways and cell cycle process were enriched in the HRisk group. Moreover, patients in the LRisk group may be more beneficial from immunotherapy. We also found that TP53 gene was more frequently mutated in the HRisk group. As for chemotherapeutic drugs commonly used in HCC, the HRisk group was highly sensitive to 5-fluorouracil, while the LRisk group presented with a significantly higher response to gefitinib and gemcitabine. Conclusion: Overall, we developed a novel DDR-related gene pair signature and nomogram to assist in predicting survival outcomes and clinical treatment of HCC patients. It also helps understand the underlying mechanisms of different DDR patterns in HCC.", "claims": [{"id": "claim-method", "statement": "Univariate Cox regression analysis and LASSO-penalized Cox regression analysis were performed to construct the DDR-related gene pair (DRGP) signature.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35496321", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Univariate Cox regression analysis and LASSO-penalized Cox regression analysis were performed to construct the DDR-related gene pair (DRGP) signature."}], "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:35496321", "locator": "sections[24] \"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 paper constructed and validated a 23 DDR-related gene-pair prognostic signature that stratified HCC patients into HRisk and LRisk groups with significantly different overall survival.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35496321", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We constructed the prognostic signature based on 23 DDR-related gene pairs."}, {"asset": "source:pmid:35496321", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The patients in the training datasets were divided into HRisk and LRisk groups at median cut-off. The HRisk group had significantly poorer OS than the LRisk group, and the signature was an independent prognostic indicator in HCC."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The paper constructed and validated a 23 DDR-related gene-pair prognostic signature that stratified HCC patients into HRisk and LRisk groups with significantly different overall survival.", "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:35496321"], "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:GSE14520"], "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:GSE14520"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35496321", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fphar.2022.857060", "sha256": "sha256:6587f7ea99be11f06f5833b5324667acea0b3d07682636b201c5aec003f62748", "bytes": 48556, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fphar.2022.857060", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9038539", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE14520", "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=GSE14520", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE14520", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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