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LNM is also taken as a sign of advanced OTSCC and poor survival rate. Recently, single\u2010cell RNA sequencing has been applied in investigating the heterogeneity of tumor microenvironment and discovering the potential biomarkers for helping the diagnosis and prognosticating. Pathogenesis of LNM in OTSCC remains unknown. Specifically, cancer\u2010associated fibroblasts (CAFs) and epithelial tumor cells could foster the progression of tumors. Thus, in this study, we aimed to comprehensively analyze the roles of subpopulations of CAFs and epithelial tumor cells in lymph node metastatic OTSCC using the integration of OTSCC single\u2010cell RNA sequencing datasets. Four distinct subtypes of CAFs, namely vascular CAFs, myofibroblast CAFs, inflammatory CAFs, and growth arrest CAFs were successfully discovered in LNM tumor and confirmed the roles of GAS and PTN pathways in the progression of tumor metastasis. In addition, NKAIN2+ epithelial cells and FN1+ epithelial cells specifically exhibited an upregulation of PTN, NRG, MIF, and SPP1 signaling pathways in the metastatic OTSCC. In doing so, we put forth some potential biomarkers that could be utilized for the purpose of diagnosing and prognosticating OTSCC during its metastatic phase and tried to confirm by immunofluorescence assays.<\/jats:p>","DOI":"10.1096\/fj.202301724r","type":"journal-article","created":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T04:46:03Z","timestamp":1704257163000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Single\u2010cell\n                    <scp>RNA<\/scp>\n                    sequencing reveals the heterogeneity of epithelial cell and fibroblast cells from non\u2010 to metastatic lymph node\n                    <scp>OTSCC<\/scp>"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5394-6746","authenticated-orcid":false,"given":"Dandan","family":"Song","sequence":"first","affiliation":[{"name":"Department of Stomatology Zhongshan Hospital, Fudan University  Shanghai 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