High YEATS2 expression promotes epithelial-mesenchymal transition in gastric cancer cells by activating the Wnt/β-catenin signaling pathway

JIANG Xuening; HUANG Qingqing; XU Ying; WANG Shunyin; ZHANG Xiaofeng; WANG Lian; WANG Yueyue; ZUO Lugen

doi:10.12122/j.issn.1673-4254.2025.11.14

Abstract：Objective To investigate YEATS2 expression in gastric cancer(GC),its prognostic value,and its regulatory role in epithelial-mesenchymal transition(EMT)of GC cells.Methods YEATS2 expression in GC was analyzed using publicly available databases.Paired GC and adjacent tissues were collected from 100 patients undergoing radical surgery for immunohistochemical detection of YEATS2 expression,and its correlations with the patients'clinicopathological parameters and Ki67 expression were analyzed.The prognostic value of YEATS2 was assessed using Kaplan-Meier analysis,Cox regression and ROC curves,and its regulatory mechanisms were analyzed using KEGG enrichment analysis.In cultured GC cell lines(HGC-27 and AGS),the effect of YEATS2 knockdown and overexpression on migration,invasion and EMT of the cells were examined with scratching assay,Transwell assay and Western blotting.Results YEATS2 was significantly overexpressed in GC tissues with a positive correlation with Ki67(P<0.05).High YEATS2 expression was associated with elevated CEA(≥5 μg/L),CA19-9(≥37 kU/L),T3-4 stage,and N2-3 stage(all P<0.05).Patients with high YEATS2 expression had significantly reduced 5-year survival(P<0.001);ROC analysis showed that YEATS2 expression levels had a sensitivity of 80.00%and a specificity of 66.67%for predicting patient survival(P<0.05).Cox regression identified high YEATS2 as an independent risk factor for poor postoperative 5-year survival outcome of GC patients(HR:1.675,95%CI:1.013-2.771;P=0.045).KEGG enrichment analysis suggested involvement of YEATS2 in EMT in GC and Wnt/β-catenin signaling.In cultured GC cells,YEATS2 overexpression significantly promoted cell migration and invasion,upregulated the expressions of vimentin,N-cadherin,Wnt and active β-catenin,and downregulated E-cadherin expression,and these changes were obviously suppressed by treatment with XAV-939(a Wnt/β-catenin inhibitor).Conclusion High YEATS2 expression activates Wnt/β-catenin signaling to promote EMT in GC and is correlated with poor prognosis of GC patients.