Immune Checkpoint Inhibitor (ICI) Genes and Aging in Clear Cell Renal Cell Carcinoma (ccRCC): Clinical and Genomic Study.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36429070", "kind": "science-record", "revision": 3, "content_hash": "sha256:08a05da7de3c69479f3c8f88ddc856b0e752e9ecd946f9544deaf06065d0b5fa", "created_at": "2026-11-01T19:00:54Z", "updated_at": "2026-11-01T22:08:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Immune Checkpoint Inhibitor (ICI) Genes and Aging in Clear Cell Renal Cell Carcinoma (ccRCC): Clinical and Genomic Study.", "doi": "10.3390/cells11223641", "pmid": "36429070", "authors": ["Abdullah Al-Danakh", "Mohammed Safi", "Mohammed Alradhi", "Qiwei Chen", "Salem Baldi", "Xinqing Zhu", "Deyong Yang"], "journal": "Cells", "year": 2022, "abstract": "Background: It is anticipated that there will be a large rise in the number of tumor diagnoses and mortality in those aged 65 and older over the course of upcoming decades. Immune checkpoint inhibitors, often known as ICIs, boost immune system activity by selectively targeting ICI genes. On the other hand, old age may be connected with unfavorable results. Methods: The Cancer Genome Atlas (TCGA) provided gene expression data from ccRCC tissue and key clinical variables. ICI gene databases were applied and verified using the GEO database. Results: We identified 14 ICI genes as risk gene signatures among 528 ccRCC patients using univariate and multivariable cox hazard models, and the elderly group was linked with poor survival. Then, by utilizing a new nomogram method, the TNFSF15 gene and age predicting values were estimated at one, three, and five years (85%, 81%, and 81%), respectively, and our age-related risk score was significant even after multivariable analysis (HR = 1.518, p = 0.009, CI = 1.1102.076). TNFSF15 gene expression was lower in elderly ccRCC patients (p = 0.0001). A negative connection between age and the TNFSF15 gene expression was discovered by correlation analysis (p = 0.0001). The verification of the gene by utilizing GEO (GSE167093) with 604 patients was obtained as external validation that showed significant differences in the TNFSF15 gene between young and elderly patients (p = 0.007). Additionally, the protein-protein interactions of the TNFSF15 gene with other ICI genes and aging-related genes was determined. In addition, the TNFSF15 expression was significantly correlated with pathological stages (p = 0.018). Furthermore, it was discovered that the biological processes of senescence, cellular senescence, the immune system, and many immune cell infiltration and immune function types are all closely tied. Conclusions: Along with the risk score evaluation, the ICI gene TNFSF15 was identified as a tumor suppressor gene related to inequalities in age survival and is associated with pathological stages and different immunity statuses. The aging responses of ccRCC patients and related gene expression need further investigation in order to identify potential therapeutic targets.", "claims": [{"id": "claim-method", "statement": "We identified prognostic genes using the univariate Cox hazard analysis method. After that, by using the survival package in the R language program, we accomplished a multivariable Cox hazard model that unveiled a score signature.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36429070", "locator": "sections[7] \"2.5. Statistical Analysis\" paragraph 2", "quote": "We identified prognostic genes using the univariate Cox hazard analysis method. After that, by using the survival package in the R language program, we accomplished a multivariable Cox hazard model that unveiled a score signature."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data in this study are open for all without need for patient consent and no require access approval. It is available in the GDC portal repository (https://portal.gdc.cancer.gov/, accessed on 5 August 2022).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36429070", "locator": "sections[21] \"notes\" paragraph 1", "quote": "All data in this study are open for all without need for patient consent and no require access approval. It is available in the GDC portal repository (https://portal.gdc.cancer.gov/, accessed on 5 August 2022)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using TCGA ccRCC data, univariate and multivariable Cox hazard models identified a 14-gene ICI risk signature associated with poor survival in elderly patients, with TNFSF15 expression lower in elderly patients.", "kind": "quantitative", "target": {"value": 0.0001, "unit": "p-value", "tolerance": null, "source": "TNFSF15 gene expression was lower in elderly ccRCC patients (p = 0.0001)."}, "evidence": [{"asset": "source:pmid:36429070", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We identified 14 ICI genes as risk gene signatures among 528 ccRCC patients using univariate and multivariable cox hazard models, and the elderly group was linked with poor survival."}, {"asset": "source:pmid:36429070", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "TNFSF15 gene expression was lower in elderly ccRCC patients (p = 0.0001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using TCGA ccRCC data, univariate and multivariable Cox hazard models identified a 14-gene ICI risk signature associated with poor survival in elderly patients, with TNFSF15 expression lower in elderly patients.", "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:36429070"], "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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