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In gastric cancer (GC), tissue\u2010derived mesenchymal stem cells (GC\u2010MSCs) critically drive tumor progression; however, the interplay between sEVs and\u00a0circRNA in GC\u2010MSCs remains incompletely understood. We identified sEVs\u2010hsa_circ_0006718 (circ6718) as significantly upregulated in gastric cancer patients. Elevated levels of sEVs\u2010circ6718 correlated with clinical stage, distant metastasis and poor prognosis, confirming its utility as both an early diagnostic and prognostic biomarker in GC. Mechanistically, circ6718 functions as a competing endogenous RNA (ceRNA) by sequestering hsa\u2010miR\u2010561\u20103p, thereby derepressing the expression of SAAL1 (Serum amyloid A\u2010like 1). SAAL1 enhances the transcriptional activity of PRRX1 (Paired related homeobox 1), which directly activates the TGF\u03b21 promoter. Consequently, the TGF\u03b21\/Smad2\/3 signaling pathway drives the transdifferentiation of GC\u2010MSCs into cancer\u2010associated fibroblasts (CAFs)\u2014promoting stromal remodeling and tumor aggressiveness. Our findings unveil a novel sEVs\u2010circRNA\u2010mediated axis in GC progression, revealing dual utility in diagnostics and targeted therapy.<\/jats:p>","DOI":"10.1002\/advs.202521334","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T21:26:41Z","timestamp":1778534801000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Small Extracellular Vesicles\u2010Derived Circ6718 Unlocks Stromal Remodeling and Serves as a Biomarker in Gastric Cancer"],"prefix":"10.1002","volume":"13","author":[{"given":"Fan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Wujin Hospital Affiliated With Jiangsu University 2 North Yongning Road Changzhou Jiangsu P. R. China"},{"name":"Jiangsu Key Laboratory of Medical Science and Laboratory Medicine Department of Laboratory Medicine School of Medicine Jiangsu University  Zhenjiang Jiangsu P. R. 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