CENPF as an independent prognostic and metastasis biomarker corresponding to CD4+ memory T cells in cutaneous melanoma.

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Skin cutaneous melanoma-upregulated genes were screened via analysis of differentially expressed genes (GSE3189 and GSE46517), and metastasis-related oncogenes were identified via weighted gene coexpression network analysis of the GSE46517 dataset. As confirmed by the Tumor Immune Estimation Resource, we found highly expressed centromere protein F (CENPF) in SKCM and its metastases. Immunostaining of human melanoma tissues demonstrated high CENPF expression. According to the Kaplan-Meier survival curve log-rank test, receiver-operating characteristic curve, and univariate and multivariate analyses, the Cancer Genome Atlas (TCGA) database suggested CENPF be a typical independent predictor of SKCM. The CIBERSORT algorithm classified the types of the immune cells from GSE46517 and showed higher proportion of CD4+ memory-activated T cells in metastatic melanoma. Single-sample gene set enrichment analysis of TCGA data confirmed the correlation between CENPF and activated CD4+ T cells. Centromere protein F was positively correlated with tumor mutational burden and CD4+ memory T cell markers (interleukin [IL]-23A, CD28, and CD62L), negatively associated with memory T cell maintenance factors (IL-7 and IL-15) by correlation analysis. Moreover, immunofluorescence showed high coexpression of CENPF and IL23A, CD4 in melanoma. Upregulated CENPF might lead to premature depletion of CD4+ memory T cells and immunosuppression. Nomogram indicated CENPF clinical predictive value for 1-, 3-, 5-, and 7-year melanoma overall survival. Therefore, CENPF plays a vital role in the progression and metastasis of melanoma and can be an effective therapeutic target.", "claims": [{"id": "claim-method", "statement": "Pearson correlation analysis was used to determine the relationship between CENPF expression and TMB.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35189004", "locator": "sections[11] \"TMB estimation and prognostic analysis\" paragraph 2", "quote": "Pearson correlation analysis was used to determine the relationship between CENPF expression and TMB."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The microarray datasets GSE3189 and GSE46517 were downloaded from the GEO database and normalized via log2 transformation for analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35189004", "locator": "sections[4] \"Differentially expressed gene (DEG) analysis\" paragraph 2", "quote": "The microarray datasets GSE3189 and GSE46517 were downloaded from the GEO database and normalized via log2 transformation for analysis."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The TCGA-based CENPF nomogram achieved a C-index of 0.683 (standard error 0.044), indicating moderate accuracy.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35189004", "locator": "sections[22] \"Centromere protein F nomogram and survival curve validation\" paragraph 4", "quote": "To evaluate the efficiency of this predictive nomogram, we calculated the C‐index of the model, which was 0.683 (with a standard error of 0.044), thereby confirming that the CENPF nomogram is moderately accurate."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The TCGA-based CENPF nomogram achieved a C-index of 0.683 (standard error 0.044), indicating moderate accuracy.", "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:35189004"], "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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