{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T18:06:09Z","timestamp":1780423569204,"version":"3.54.1"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Diabetic retinopathy (DR), a major microvascular complication of diabetes and leading global blindness cause, involves uric acid (UA) in its onset and progression. This study aimed to identify UA-related genes (UARGs) in DR and clarify their molecular mechanisms for improved diagnosis and treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using public database transcriptome data, key UARGs were screened via differential expression analysis, machine learning, receiver operating characteristic (ROC) analysis, and expression profiling, followed by gene set enrichment analysis (GSEA), immune infiltration analysis, molecular regulatory network construction, and clinical validation with reverse transcription quantitative polymerase chain reaction (RT-qPCR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>MMP15<\/jats:italic>\n                      and\n                      <jats:italic>FOXK1<\/jats:italic>\n                      were identified as potential key genes, with significantly elevated expression in DR patient blood samples. GSEA showed\n                      <jats:italic>MMP15<\/jats:italic>\n                      enriched in Apc targets requiring Myc and Smarca2 targets up, and\n                      <jats:italic>FOXK1<\/jats:italic>\n                      in phosphatidylinositol signaling system and proteasome. Immune infiltration analysis revealed differences in 7 immune cell types, with central memory CD8 T cells and natural killer cells showing the strongest positive correlation;\n                      <jats:italic>MMP15<\/jats:italic>\n                      was negatively correlated with NK cells, and\n                      <jats:italic>FOXK1<\/jats:italic>\n                      with central memory CD4 T cells and effector memory CD8 T cells. Twelve transcription factors (e.g., HOXB7, CATA6) jointly targeted both genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>MMP15<\/jats:italic>\n                      and\n                      <jats:italic>FOXK1<\/jats:italic>\n                      were identified as potential key genes associated with uric acid in DR, which may provide a reference for further exploration of the pathogenesis and targeted therapy of DR.\n                    <\/jats:p>\n                  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