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OSF is a well\u2010established precancerous lesion, and a portion of OSF cases eventually progress to oral squamous cell carcinoma (OSCC). However, the specific molecular mechanisms underlying the malignant transformation of OSCC from OSF are poorly understood. In this study, the leading\u2010edge techniques of Spatial Transcriptomics (ST) and Spatial Metabolomics (SM) are integrated to obtain spatial location information of cancer cells, fibroblasts, and immune cells, as well as the transcriptomic and metabolomic landscapes in OSF\u2010derived OSCC tissues. This work reveals for the first time that some OSF\u2010derived OSCC cells undergo partial epithelial\u2013mesenchymal transition (pEMT) within the in situ carcinoma (ISC) region, eventually acquiring fibroblast\u2010like phenotypes and participating in collagen deposition. Complex interactions among epithelial cells, fibroblasts, and immune cells in the tumor microenvironment are demonstrated. Most importantly, significant metabolic reprogramming in OSF\u2010derived OSCC, including abnormal polyamine metabolism, potentially playing a pivotal role in promoting tumorigenesis and immune evasion is discovered. The ST and SM data in this study shed new light on deciphering the mechanisms of OSF\u2010derived OSCC. The work also offers invaluable clues for the prevention and treatment of OSCC.<\/jats:p>","DOI":"10.1002\/advs.202306515","type":"journal-article","created":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T23:25:40Z","timestamp":1705447540000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Spatial Transcriptomic and Metabolomic Landscapes of Oral Submucous Fibrosis\u2010Derived Oral Squamous Cell Carcinoma and its Tumor Microenvironment"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0307-8727","authenticated-orcid":false,"given":"Yuan","family":"Zhi","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery The Second Xiangya Hospital of Central South University  Changsha Hunan 410011 China"},{"name":"NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of 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