Characterization of a G2M checkpoint-related gene model and subtypes associated with immunotherapy response for clear cell renal cell carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38617927", "kind": "science-record", "revision": 3, "content_hash": "sha256:e37405fe18bed75d3a35ec4a9a38d3b31629f444fa30f6ad625908298cadd203", "created_at": "2026-11-01T19:20:35Z", "updated_at": "2026-11-01T22:11:41Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Characterization of a G2M checkpoint-related gene model and subtypes associated with immunotherapy response for clear cell renal cell carcinoma.", "doi": "10.1016/j.heliyon.2024.e29289", "pmid": "38617927", "authors": ["Zhenwei Wang", "Zongtai Zheng", "Bangqi Wang", "Changxin Zhan", "Xuefeng Yuan", "Xiaoqi Lin", "Qifan Xin", "Zhihui Zhong", "Xiaofu Qiu"], "journal": "Heliyon", "year": 2024, "abstract": "Clear cell renal cell carcinoma (ccRCC) presents challenges in early diagnosis and effective treatment. In this study, we aimed to establish a prognostic model based on G2M checkpoint-related genes and identify associated clusters in ccRCC through clinical bioinformatic analysis and experimental validation. Utilizing a single-cell RNA dataset (GSE159115) and bulk-sequencing data from The Cancer Genome Atlas (TCGA) database, we analyzed the G2M checkpoint pathway in ccRCC. Differential expression analysis identified 45 genes associated with the G2M checkpoint, leading to the construction of a predictive model with four key genes (E2F2, GTSE1, RAD54L, and UBE2C). The model demonstrated reliable predictive ability for 1-, 3-, and 5-year overall survival, with AUC values of 0.794, 0.790, and 0.794, respectively. Patients in the high-risk group exhibited a worse prognosis, accompanied by significant differences in immune cell infiltration, immune function, TIDE and IPS scores, and drug sensitivities. Two clusters of ccRCC were identified using the \"ConsensusClusterPlus\" package, cluster 1 exhibited a worse survival rate and was resistant to chemotherapeutic drugs of Axitinib, Erlotinib, Pazopanib, Sunitinib, and Temsirolimus, but not Sorafenib. Targeted experiments on RAD54L, a gene involved in DNA repair processes, revealed its crucial role in inhibiting proliferation, invasion, and migration in 786-O cells. In conclusion, our study offers valuable insights into the molecular mechanisms underlying ccRCC, identifying potential prognostic genes and molecular subtypes associated with the G2M checkpoint. These findings hold promise for guiding personalized treatment strategies in the management of ccRCC.", "claims": [{"id": "claim-method", "statement": "Kaplan-Meier (K-M) survival analysis and time-dependent receiver operating characteristic (ROC) analysis based on OS were performed to assess the prognostic accuracy of the gene signature.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38617927", "locator": "sections[4] \"Enrichment analysis of G2M pathway in ccRCC\" paragraph 6", "quote": "Kaplan-Meier (K-M) survival analysis and time-dependent receiver operating characteristic (ROC) analysis based on OS were performed to assess the prognostic accuracy of the gene signature."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The public cohort datasets collected in the present study are available online on the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) websites. Additional data could be available upon request to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38617927", "locator": "sections[28] \"Data availability statement\" paragraph 2", "quote": "The public cohort datasets collected in the present study are available online on the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) websites. Additional data could be available upon request to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The four-gene prognostic model demonstrated reliable predictive ability for 1-, 3-, and 5-year overall survival, with AUC values of 0.794, 0.790, and 0.794, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38617927", "locator": "sections[18] \"GMCRGs model associates with OS of ccRCC in the training and testing cohorts\" paragraph 2", "quote": "To evaluate the predictive capability of our prognostic model, ROC curves were employed, yielding AUC values of 0.794, 0.790, and 0.794 for 1-, 3-, and 5-year overall survival, respectively (Fig. 3E)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The four-gene prognostic model demonstrated reliable predictive ability for 1-, 3-, and 5-year overall survival, with AUC values of 0.794, 0.790, and 0.794, 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:38617927"], "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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Cell culture and transfection We purchased the human renal cortex proximal", "he786-O. The cells were harvested 48 h after transfection for further experimentation. The sequences o", "ent using a cell incubator. RAD54L-targeting siRNA constructs and si-NC (non-targeting control)", "vitrogen, USA) was employed to introduce the siRNA constructs into the786-O. The cells were har"], "order_basis": "paper_text_order:4915", "id": "assay:1"}, {"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": ["m the Chinese Academy of Sciences. The three cell lines were cultured in 1640 medium (Gibco, New York, NY, USA) su", "ademy of Sciences. 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