SDCBP的泛癌分析及其对胃癌细胞增殖迁移的影响OA

Objective·To systematically assess the expression characteristics and prognostic significance of syndecan-binding protein(SDCBP)across various cancers,as well as its associations with the tumor immune microenvironment,tumor mutational burden(TMB),and drug sensitivity,and to validate the biological functions and underlying mechanisms of SDCBP in gastric cancer through in vitro experiments.Methods·This study conducted comprehensive multi-omics analyses to examine the differential expression,prognostic indicators,immune infiltration,immune checkpoints,TMB/microsatellite instability(MSI),and drug sensitivity associated with SDCBP by integrating data from various bioinformatics databases.In addition,Western blotting,cell counting kit-8(CCK-8)assay,wound healing assay,and Transwell assay were utilized to assess the impact of SDCBP on the proliferation and migration of gastric cancer cells,and to elucidate its regulatory roles in epithelial-mesenchymal transition(EMT)-related proteins and the TGF-β/Smad signaling pathway.Results·SDCBP expression was significantly upregulated in various malignant tumors,including gastric cancer,and its high expression was closely associated with poor prognosis(all P<0.05).Additionally,SDCBP expression levels exhibited a positive correlation with diverse immune-infiltrating cells,immune regulatory factors,and major histocompatibility complex(MHC)molecules.Furthermore,in certain tumors,SDCBP expression was significantly associated with TMB or MSI(all P<0.05).Drug sensitivity analysis revealed that elevated SDCBP expression was positively correlated with tumor drug resistance,and in specific cancer types,negatively correlated with intratumoral microbial abundance(all P<0.05).In vitro experiments provided further evidence that SDCBP was highly expressed in gastric cancer tissues and cell lines.SDCBP expression was significantly reduced in patients older than 65 years(P<0.05).Furthermore,SDCBP expression levels differed significantly across TNM stages(Ⅰ‒ Ⅳ),with stage Ⅲ exhibiting the highest expression(P<0.05).According to Lauren classification,diffuse-type tumors exhibited significantly higher SDCBP expression compared to intestinal-type and mixed-type tumors(P<0.05).Furthermore,molecular subtype analysis indicated that SDCBP expression was significantly greater in the invasive subtype than in other subtypes(P<0.001).The silencing of SDCBP inhibited the viability and migration of gastric cancer cells,whereas its overexpression facilitated the malignant phenotypes of these cells(P<0.05).Mechanistic investigations suggested that SDCBP may advance the progression of gastric cancer by modulating the expression of EMT-related proteins,including N-cadherin,Vimentin,and Snail1(P<0.05),and by activating the TGF-β/Smad signaling pathway.Conclusion·SDCBP has important clinical relevance across pan-cancer types and may serve as a key molecule promoting gastric cancer progression,providing theoretical support for its potential role as a prognostic biomarker and therapeutic target.