Immune checkpoint inhibitor (ICI) genes and aging in malignant melanoma patients: a clinicogenomic TCGA study.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36100891", "kind": "science-record", "revision": 5, "content_hash": "sha256:904b4756747fdf372a639d24bfbc563f4e3220ee2029e57160b80c263e3ebed0", "created_at": "2026-11-01T18:15:20Z", "updated_at": "2026-11-01T22:50:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Immune checkpoint inhibitor (ICI) genes and aging in malignant melanoma patients: a clinicogenomic TCGA study.", "doi": "10.1186/s12885-022-09860-2", "pmid": "36100891", "authors": ["Mohammed Safi", "Chenxing Jin", "Abdullah Aldanakh", "Ping Feng", "Henan Qin", "Mohammed Alradhi", "Lizhi Zhang", "Junying Zhang", "Salah Adlat", "Yi Zhao", "Jiwei Liu"], "journal": "BMC cancer", "year": 2022, "abstract": "BACKGROUND: Cancer diagnoses and deaths among the elderly (65 +) are expected to increase significantly over the next decade. Immune checkpoint inhibitors specifically target ICI genes and enhance immune system function. However, poor outcomes may be associated with aging.\nMETHODS: We downloaded the Genomic Data Commons from the Cancer Genome Atlas (TCGA) and collected gene expression data from malignant melanoma (MM) tissues, the third level as the primary site. The CKTTD ICI genes database were applied and validated using the GEO database and lab experiments.\nRESULTS: In 414 patients, 13 ICI genes were obtained as risk gene signature by univariate and multivariate Cox hazard models and were associated with poor survival in the older group. At 1, 3, and 5 years (79%, 76%, and 76%, respectively), we investigate TNFRFS4 gene and age prediction using novel nomogram-associated aging (HR = 1.79, P 0.001, CI = 1.32-2.45) with higher sensitivity testing.TNFRSF4 gene expression was significantly high in younger (15 years interval) MM patients (P < 0.001). By correlation analysis, a significant negative association was determined (P < 0.001). The validation of gene correlation from GEO (GSE59455) and (GSE22153) was obtained as external validation. We tested the TNFRSF4 protein levels by IHC in 14 melanoma tissue samples. TNFRSF4 expression was observed to be lower expressed in the older of melanoma tissues, and higher in the younger age group (P = 0.02). Besides the connectivity of ICI gene proteins, the biological processes of cell aging, aging, and the immune system were found to be highly related.\nCONCLUSIONS: Along with the risk score evaluation, the ICI gene (TNFRSF4) was identified as a tumor suppressor gene related to inequalities in age survival and associated with immune cell infiltrations. The aging responses of melanoma patients and related gene expression need further investigation in order to identify potential therapeutic targets.", "claims": [{"id": "claim-method", "statement": "Independent tests, one-way ANOVA on ranks, and correlation analysis were also applied.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36100891", "locator": "sections[5] \"Statistical analysis\" paragraph 2", "quote": "Independent tests, one-way ANOVA on ranks, and correlation analysis were also applied."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analysed during the current study are available in the GDC portal repository, [https://portal.gdc.cancer.gov/].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36100891", "locator": "sections[22] \"notes\" paragraph 1", "quote": "The datasets generated and/or analysed during the current study are available in the GDC portal repository, [https://portal.gdc.cancer.gov/]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "TNFRSF4 gene expression was negatively correlated with age in the TCGA training cohort and was externally validated in GEO datasets GSE59455 and GSE22153 (P < 0.0001, r = -0.20, P = 0.01, r = -0.24, respectively).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36100891", "locator": "sections[11] \"Ageing-related genes\" paragraph 3", "quote": "In addition to the correlation analysis in the training group, validation of gene correlation from GEO (GSE59455) and (GSE22153) were obtained as external validation. ((P < 0.0001) and r = -0.20, P = 0.01, r = -0.24) respectively (Fig. 5)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "TNFRSF4 gene expression was negatively correlated with age in the TCGA training cohort and was externally validated in GEO datasets GSE59455 and GSE22153 (P < 0.0001, r = -0.20, P = 0.01, r = -0.24, 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:36100891"], "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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We tested the TNFRSF4 protein levels by IHC in 14 melanoma tissue samples. TNFRSF4 expre", ".4 and SPSS version 25. Experimental methods Immunohistochemistry (IHC) We used the hematoxylin and eosin (H&E", ". Experimental methods Immunohistochemistry (IHC) We used the hematoxylin and eosin (H&E) sta", "e protein expression levels of TNFRSF4 using IHC We tested the TNFRSF4 protein levels by IHC"], "order_basis": "paper_text_order:1366", "id": "assay:1"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Independent tests, one-way ANOVA on ranks, and correlation analysis were also applied."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}