SLPI as a dedifferentiation biomarker in BRAFV600E-mutant papillary thyroid cancer.

ABSTRACT: The BRAFV600E mutation drives papillary thyroid carcinoma (PTC) progression and therapy resistance, yet its downstream effectors remain incompletely characterized. Here, we identify secretory leukocyte protease inhibitor (SLPI) as a novel dedifferentiation biomarker in BRAFV600E-mutant PTC through integrated multi-omics analyses and functional validation. SLPI expression was significantly elevated in BRAFV600E-mutant tumors and correlated with advanced TNM stage, lymph node metastasis, and poor survival. Its overexpression was caused mechanistically by AP-1 transactivation and SLPI promoter hypomethylation. SLPI knockdown in PTC cells suppressed proliferation, increased anoikis sensitivity, and reduced FAK/AKT phosphorylation. Enrichment analysis linked high SLPI expression to PI3K/AKT pat

SUBMITTER: Luo W 

PROVIDER: S-EPMC12358826 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature