{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T18:15:46Z","timestamp":1772993746054,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FASEB BioAdvances"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The cellular and molecular complexity of acne pathogenesis has hindered progress toward effective targeted therapies. While keratinocytes are known to influence skin inflammation, their precise transcriptional programs and regulatory circuitry in acne remain unclear. We developed an integrative computational framework that combines single\u2010cell RNA sequencing (scRNA\u2010seq), gene co\u2010expression network analysis (WGCNA), and two complementary machine learning algorithms (SVM\u2010RFE, LASSO) to identify disease\u2010relevant biomarkers. We mapped acne lesion cellular composition, reconstructed keratinocyte differentiation trajectories, and integrated miRNA\u2013transcription factor\u2013drug interaction networks to link molecular signatures to potential interventions. We uncovered marked keratinocyte heterogeneity and enriched late\u2010stage pro\u2010inflammatory states in acne lesions, accompanied by increased macrophage\/monocyte and T cell infiltration. Six keratinocyte\u2010associated biomarkers (PYGL, C10orf99, C12orf75, S100A2, PI3, CARD18) were identified, achieving high diagnostic accuracy (AUC &gt;\u20090.85). Functional enrichment connected these genes to cytokine and chemokine signaling, while regulatory analysis revealed upstream modulators (hsa\u2010let\u20107b\u20105p, FOXC1). Drug\u2013gene network mapping suggested repurposing potential for cyclosporin A and valproic acid. In conclusion, our study delineates a keratinocyte\u2010centered molecular signature that shapes acne pathogenesis and provides potential therapeutic biomarkers.<\/jats:p>","DOI":"10.1096\/fba.2025-00255","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T14:26:24Z","timestamp":1770128784000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Keratinocyte\u2010Associated Biomarkers Reveal Pathogenic Mechanisms in Acne"],"prefix":"10.1096","volume":"8","author":[{"given":"Sini","family":"Cai","sequence":"first","affiliation":[{"name":"Medical Cosmetic Center of Dermatology Hospital of Southern Medical University, Guangdong Provincial Dermatology Hospital  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinjing","family":"Lin","sequence":"additional","affiliation":[{"name":"Medical Cosmetic Center of Dermatology Hospital of Southern Medical University, 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