Pan-Cancer Analysis Confirms the Prognostic and Immunological Implications of the 1,25-Dihydroxy Vitamin D3 Receptor in Cervical Squamous Cell Carcinoma.

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A pan-cancer analysis was conducted on VDR in CESC, with a focus on its expression and relationship with immune infiltration and genetic alterations. Bioinformatics databases, including TIMER, GEPIA, UALCAN, cBioportal, and Kaplan-Meier Plotter, have been utilized. VDR expression in CESC has been validated using publicly available data. Results were significantly upregulated (P=0.05) in THCA, BRCA, KICH, LUAD, LIHC, STAD, UCEC, CESC, CHOL, ESCA, and HNSC samples. We analyzed the correlation between VDR expression and various clinicopathological factors such as age, race, and cancer stage. VDR expression was significantly upregulated across all age groups, with the highest levels observed in older adults followed by young and middle-aged adults. VDR gene expression was significantly elevated across all races, including Caucasians, African-Americans, and Asians, compared to that in the normal group. Furthermore, VDR expression was significantly upregulated in cancer stages 1, 2, 3, and 4, with the highest increase observed in stage 3 compared to that in normal individuals. We analyzed the expression of the VDR in relation to immune cell type and tumor cell purity in CESC. Our results indicated that VDR expression was positively correlated with neutrophils and dendritic cells and negatively correlated with tumor cell purity in CESC patients. There was no significant correlation between VDR expression and the abundance of B cells, CD8+ T cells, CD4+ T cells, and macrophages. Our study found no significant effect of VDR expression on patient prognosis, although it was positively correlated with CD4+ T cells. The Cox proportional hazards model indicated that age and immune cells did not significantly affect prognosis. Most VDR mutations are concentrated in diffuse large B-cell lymphoma, with an amplification frequency of 4% and a deep deletion frequency of 2.2%. GEO confirmed VDR expression in CESC, identifying 1515 upregulated and 1877 downregulated genes, with volcano plots showing CESC downregulation in patients.", "claims": [{"id": "claim-method", "statement": "According to the Cox proportional hazards model, age and immune cells were not significantly associated with prognosis (Table 1).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39268267", "locator": "sections[3] \"Results\" paragraph 22", "quote": "According to the Cox proportional hazards model, age and immune cells were not significantly associated with prognosis (Table 1)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The TIMER database provides computational biologists with the ability to analyze the association between gene expression and the abundance of immune infiltrates in various cancers [7].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39268267", "locator": "sections[2] \"Materials and methods\" paragraph 4", "quote": "The TIMER database provides computational biologists with the ability to analyze the association between gene expression and the abundance of immune infiltrates in various cancers [7]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In CESC, VDR expression was positively correlated with neutrophils and dendritic cells and negatively correlated with tumor cell purity, but was not significantly correlated with B cells, CD8+ T cells, CD4+ T cells, or macrophages.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39268267", "locator": "sections[3] \"Results\" paragraph 16", "quote": "In CESC patients, VDR expression was positively correlated with neutrophils (Cor=0.229, P=1.18e-04) and dendritic cells (Cor=0.245, P=3.86e-05) and negatively correlated with tumor cell purity, but not with the abundance of B cells, CD8+ T cells, CD4+ T cells, and macrophages (Figure 7)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In CESC, VDR expression was positively correlated with neutrophils and dendritic cells and negatively correlated with tumor cell purity, but was not significantly correlated with B cells, CD8+ T cells, CD4+ T cells, or macrophages.", "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:39268267"], "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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