A novel DNA damage repair-related gene signature predicting survival, immune infiltration and drug sensitivity in cervical cancer based on single cell sequencing.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37449209", "kind": "science-record", "revision": 4, "content_hash": "sha256:9cb5cedcd90d461cf13b510ae5f09d6f14277130180f285edeee46e927c6d1e5", "created_at": "2026-11-01T19:02:13Z", "updated_at": "2026-11-01T22:09:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A novel DNA damage repair-related gene signature predicting survival, immune infiltration and drug sensitivity in cervical cancer based on single cell sequencing.", "doi": "10.3389/fimmu.2023.1198391", "pmid": "37449209", "authors": ["Xiaoqing Xiang", "Jiawen Kang", "Jingwen Jiang", "Yaning Zhang", "Yong Zhang", "Lesai Li", "Xiaoning Peng"], "journal": "Frontiers in immunology", "year": 2023, "abstract": "Background: Aberrant DNA damage repair (DDR) is one of the hallmarks of tumors, and therapeutic approaches targeting this feature are gaining increasing attention. This study aims to develop a signature of DDR-related genes to evaluate the prognosis of cervical cancer (CC).\nMethods: Differentially expressed genes were identified between high and low DDR groups of cells from the single-cell RNA sequencing dataset GSE168652 based on DDR scores. Using the ssGSEA and WGCNA methods, DDR-related differentially expressed genes were identified from different patients within the TCGA-CESC cohort. Using Cox analysis and LASSO regression analysis, a DDR-related gene signature was constructed based on the intersection of two groups of differentially expressed genes and DDR-related genes from WGCNA, and validated in GSE52903. Immune cell infiltration analysis, mutation analysis, survival analysis, drug sensitivity analysis, etc., were performed in different groups which were established based on the DDR gene signature scoring. A key gene affecting prognosis was selected and validated through biological experiments such as wound healing, migration, invasion, and comet assays.\nResults: A novel DDR-related signature was constructed and the nomogram results showed this signature performed better in predicting prognosis than other clinical features for CC. The high DDR group exhibited poorer prognosis, weaker immune cell infiltration in the immune microenvironment, lower expression of immune checkpoint-related genes, lower gene mutation frequencies and more sensitivity to drugs such as BI.2536, Bleomycin and etc. ITGB1, ZC3H13, and TOMM20 were expressed at higher levels in CaSki and HeLa cells compared to ECT1 cells. Compared with the native CaSki and HeLa cells, the proliferation, migration, invasion and DDR capabilities of CaSki and HeLa cell lines with ITGB1 suppressed expression were significantly decreased.\nConclusion: The 7 DDR-related gene signature was an independent and powerful prognostic biomarker that might effectively evaluate the prognosis of CC and provide supplementary information for a more personalized evaluation and precision therapy. ITGB1 was a potential candidate gene that may affect the DDR capacity of CC cells, and its mechanism of action was worth further in-depth study.", "claims": [{"id": "claim-method", "statement": "We performed univariate Cox analysis on the intersection genes of the gene sets related to DDR obtained from WGCNA analysis and the gene sets obtained from single-cell differential expression analysis. To avoid overfitting, the “glmnet (version 4.1-4)” package was used for Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis to construct a prognostic DDR-related gene signature.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37449209", "locator": "sections[8] \"Construction and validation of the prognostic signature associated with DDR\" paragraph 2", "quote": "We performed univariate Cox analysis on the intersection genes of the gene sets related to DDR obtained from WGCNA analysis and the gene sets obtained from single-cell differential expression analysis. To avoid overfitting, the “glmnet (version 4.1-4)” package was used for Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis to construct a prognostic DDR-related gene 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:37449209", "locator": "sections[34] \"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 AUC values of the signature in 1, 2, 3, and 5 years were 0.644, 0.724, 0.724, and 0.736, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37449209", "locator": "sections[23] \"Construction and validation of DDR-related prognostic signature\" paragraph 3", "quote": "The AUC values of the signature in 1, 2, 3, and 5 years were 0.644, 0.724, 0.724, and 0.736, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The AUC values of the signature in 1, 2, 3, and 5 years were 0.644, 0.724, 0.724, and 0.736, 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:37449209"], "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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Using"], "order_basis": "paper_text_order:499", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["low DDR groups of cells from the single-cell RNA sequencing dataset GSE168652 based on DDR scores. Using"], "order_basis": "paper_text_order:511", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["were expressed at higher levels in CaSki and HeLa cells compared to ECT1 cells. Compared with", "T1 cells. Compared with the native CaSki and HeLa cells, the proliferation, migration, invasio", ", invasion and DDR capabilities of CaSki and HeLa cell lines with ITGB1 suppressed expression", "echnology Development Co. HeLa and ECT1 were cultured in DMEM medium (Procell, Wuhan, China) suppleme"], "order_basis": "paper_text_order:1812", "id": "assay:3"}, {"role": "data_generation", "definition_id": "methylation_array", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["of immune-related algorithms (“CIBERSORT”, “EPIC”, “MCP_counter”, “xCell”, “TIMER”, “Quanti-s"], "order_basis": "paper_text_order:3148", "id": "assay:4"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["roups and drug sensitivity. Cell culture and transfection HeLa cells derived from human cervical adeno", "phase for subsequent experiments. Cells were transfected with the previously synthesized sh-ITGB1 (Ge", "em Inc, Shanghai, China) using the Lipo8000™ Transfection Reagent (Beyotime Biotechnology, Shanghai, M", "nt experiments were performed 48 hours after transfection of the cells. The shRNA sequences for ITGB1"], "order_basis": "paper_text_order:4899", "id": "assay:5"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["limma"], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}