Identification of Pyroptosis-Relevant Signature in Tumor Immune Microenvironment and Prognosis in Skin Cutaneous Melanoma Using Network Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36818162", "kind": "science-record", "revision": 3, "content_hash": "sha256:f1dfa0a200b10c616ddacc516f992659b23e8c2cc11fd014fa930f5819882a3f", "created_at": "2026-11-01T19:01:24Z", "updated_at": "2026-11-01T22:08:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Pyroptosis-Relevant Signature in Tumor Immune Microenvironment and Prognosis in Skin Cutaneous Melanoma Using Network Analysis.", "doi": "10.1155/2023/3827999", "pmid": "36818162", "authors": ["Yun Zhu", "Dan Han", "Hongjue Duan", "Qi Rao", "Yike Qian", "Qiaoyun Chen", "Xiao Du", "Huanyu Ni", "Siliang Wang"], "journal": "Stem cells international", "year": 2023, "abstract": "Background: Pyroptosis is closely related to the programmed death of cancer cells as well as the tumor immune microenvironment (TIME) via the host-tumor crosstalk. However, the role of pyroptosis-related genes as prognosis and TIME-related biomarkers in skin cutaneous melanoma (SKCM) patients remains unknown.\nMethods: We evaluated the expression profiles, copy number variations, and somatic mutations (CNVs) of 27 genes obtained from MSigDB database regulating pyroptosis among TCGA-SKCM patients. Thereafter, we conducted single-sample gene set enrichment analysis (ssGSEA) for evaluating pyroptosis-associated expression patterns among cases and for exploring the associations with clinicopathological factors and prognostic outcome. In addition, a prognostic pyroptosis-related signature (PPRS) model was constructed by performing Cox regression, weighted gene coexpression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO) analysis to score SKCM patients. On the other hand, we plotted the ROC and survival curves for model evaluation and verified the robustness of the model through external test sets (GSE22153, GSE54467, and GSE65904). Meanwhile, we examined the relations of clinical characteristics, oncogene mutations, biological processes (BPs), tumor stemness, immune infiltration degrees, immune checkpoints (ICs), and treatment response with PPRS via multiple methods, including immunophenoscore (IPS) analysis, gene set variation analysis (GSVA), ESTIMATE, and CIBERSORT. Finally, we constructed a nomogram incorporating PPRS and clinical characteristics to improve risk evaluation of SKCM.\nResults: Many pyroptosis-regulated genes showed abnormal expression within SKCM. TP53, TP63, IL1B, IL18, IRF2, CASP5, CHMP4C, CHMP7, CASP1, and GSDME were detected with somatic mutations, among which, a majority displayed CNVs at high frequencies. Pyroptosis-associated profiles established based on pyroptosis-regulated genes showed markedly negative relation to low stage and superior prognostic outcome. Blue module was found to be highly positively correlated with pyroptosis. Later, this study established PPRS based on the expression of 8 PAGs (namely, GBP2, HPDL, FCGR2A, IFITM1, HAPLN3, CCL8, TRIM34, and GRIPAP1), which was highly associated with OS, oncogene mutations, tumor stemness, immune infiltration degrees, IC levels, treatment responses, and multiple biological processes (including cell cycle and immunoinflammatory response) in training and test set samples.\nConclusions: Based on our observations, analyzing modification patterns associated with pyroptosis among diverse cancer samples via PPRS is important, which can provide more insights into TIME infiltration features and facilitate immunotherapeutic development as well as prognosis prediction.", "claims": [{"id": "claim-method", "statement": "Subsequently, univariate Cox regression was performed to search prognostic PAGs. Additionally, LASSO Cox regression was conducted to establish the PPRS with the least risk of overfitting.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36818162", "locator": "sections[8] \"2.6. Establishment and Estimation of PPRS for Prognosis Prediction of SKCM\" paragraph 2", "quote": "Subsequently, univariate Cox regression was performed to search prognostic PAGs. Additionally, LASSO Cox regression was conducted to establish the PPRS with the least risk of overfitting."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The dataset used in this study is available in GSE22153 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22153), GSE54467 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54467), and GSE65904 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65904).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36818162", "locator": "sections[23] \"Data Availability\" paragraph 2", "quote": "The dataset used in this study is available in GSE22153 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22153), GSE54467 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54467), and GSE65904 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65904)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study established an 8-PAG prognostic pyroptosis-related signature (PPRS) that was highly associated with overall survival and multiple clinical, molecular, stemness, immune, and treatment-response features.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36818162", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Later, this study established PPRS based on the expression of 8 PAGs (namely, GBP2, HPDL, FCGR2A, IFITM1, HAPLN3, CCL8, TRIM34, and GRIPAP1), which was highly associated with OS, oncogene mutations, tumor stemness, immune infiltration degrees, IC levels, treatment responses, and multiple biological processes (including cell cycle and immunoinflammatory response) in training and test set samples."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study established an 8-PAG prognostic pyroptosis-related signature (PPRS) that was highly associated with overall survival and multiple clinical, molecular, stemness, immune, and treatment-response features.", "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:36818162"], "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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