Integrated single-cell and functional analyses define fatty acid oxidation activation associates with poor prognosis in oral squamous cell carcinoma

Integrated single-cell and functional analyses define fatty acid oxidation activation associates with poor prognosis in oral squamous cell carcinoma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Integrated single-cell and functional analyses define fatty acid oxidation activation associates with poor prognosis in oral squamous cell carcinoma Huiting Hu, Hongxing Chu, Zhenzhen Wu, Zekun Gan, Yong Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9139378/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Fatty acid oxidation (FAO) activation was reported to promote tumor progression, yet its role in oral squamous cell carcinoma (OSCC) remains incompletely understood. Here, we found that FAO was significantly activated in both OSCC tissue biopsies and OSCC cell lines. Public single-cell RNA sequencing revealed FAO activity was remarkably heterogeneous across distinct cell populations within the tumor microenvironment of OSCC. FAO-high cells laid a greater emphasis on energetic metabolism, whereas FAO-low cells showed activated immune responses. Furthermore, an effective FAO-based prognostic model was established via leveraging 101 machine learning algorithms on 4 different patient cohorts, which suggested high-FAO activity closely correlated with poor outcomes. Finally, experimental validation supported pharmacological inhibition of FAO aggravated mitochondrial energy metabolism dysfunction and promoted apoptosis of OSCC cell lines. Our findings provide novel insights into the function of FAO in OSCC and offer a potential therapeutic strategy for retarding OSCC progression. FAO OSCC Single-cell RNA sequencing Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementaltable1.xlsx Supplementaltable2.xlsx Supplementaltable3.xlsx Supplementalmaterials.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 18 May, 2026 Reviews received at journal 06 May, 2026 Reviewers agreed at journal 06 May, 2026 Reviewers agreed at journal 05 May, 2026 Reviewers invited by journal 28 Apr, 2026 Editor assigned by journal 08 Apr, 2026 Submission checks completed at journal 03 Apr, 2026 First submitted to journal 03 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9139378","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":635126367,"identity":"8b0c826b-a97c-4d5f-a50b-01c810bbd92b","order_by":0,"name":"Huiting Hu","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Huiting","middleName":"","lastName":"Hu","suffix":""},{"id":635126369,"identity":"492f1d07-0596-4b87-b685-93f0592ecd38","order_by":1,"name":"Hongxing Chu","email":"","orcid":"","institution":"Southern Medical 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