SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma.

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A total of 80 patients with UM from TCGA were assigned to two groups based on the metastatic status, and bioinformatic analyses were performed to search for critical genes for risk of metastasis. SLC25A38, located on chromosome 3, was the dominant downregulated gene in metastatic UM patients. Low expression of SLC25A38 was an independent predictive and prognostic factor in UM. The predictive potential of SLC25A38 expression was superior to that of pervious reported biomarkers in both TCGA cohort and GSE22138 cohort. Subsequently, its role in promoting metastasis was explored in vitro and in vivo. Knock-out of SLC25A38 could enhance the migration ability of UM cells, and promote distant metastasis in mice models. Through the inhibition of CBP/HIF-mediated pathway followed by the suppression of pro-angiogenic factors, SLC25A38 was situated upstream of metastasis-related pathways, especially angiogenesis. Low expression of SLC25A38 promotes angiogenesis and metastasis, and identifies increased metastatic risk and worse survival in UM patients. This finding may further improve the accuracy of prognostic prediction for UM.", "claims": [{"id": "claim-method", "statement": "Univariate and multivariate analyses were performed using Cox regression analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35411037", "locator": "sections[12] \"Bioinformatic and statistical analyses\" paragraph 3", "quote": "Univariate and multivariate analyses were performed using Cox regression analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analyzed during this study are included in this published article and its supplementary information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35411037", "locator": "sections[25] \"Data availability\" paragraph 2", "quote": "All data generated or analyzed during this study are included in this published article and its supplementary information files."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "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:35411037"], "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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