TEAD4 functions as a prognostic biomarker and triggers EMT via PI3K/AKT pathway in bladder cancer

作者：Ming Chi, Jiao Liu, Chenxue Mei, Yaxing Shi, Nanqi Liu, Xuefeng Jiang, Chang Liu, Nan Xue, Hong Hong, Jisheng Xie, Xun Sun, Bo Yin, Xin Meng, Biao Wang · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2022 · DOI：10.1186/s13046-022-02377-3 · 被引用次数：174 · 研究领域：Hippo pathway signaling and YAP/TAZ、Cancer-related gene regulation、Cancer-related molecular mechanisms research

BACKGROUND: The distant metastasis is the primary cause of cancer morbidity and mortality for bladder cancer (BLCA) paitents. All the recommended therapy for it largely depends on how far the cancer has invaded. It has been confirmed that epithelial to mesenchymal transition (EMT) is the leading reason for the BLCA metastasis which makes BLCA difficult to cure. The aim of the present study is to identify the BLCA-related genes that can be used as the new prognostic biomarker and treatment target, and to investigate the functional mechanisms of TEAD4 in EMT dysregulation. METHODS: The "limma" R package was used to identify the differentially expressed genes (DEGs) between the normal and the tumor samples from TCGA BLCA and GTEx databases. Kaplan-Meier and UniCox analysis were used to filter DEGs with prognostic value in BLCA. Step muti-Cox analysis was used to construct a prognostic risk score model based on clinical phenotype characters. Gene set enrichment analysis (GSEA) was performed to explore the possible molecular mechanisms affecting the prognosis in BLCA. Unsupervised hierarchical clustering analysis was performed to evaluate the effects of EMT process on the prognosis. Single-sample GSEA (ssGSEA) was used to calculate the correlation betweeen the expression of DEGs and EMT enrichment scores. TEAD4 expression and its association with pathological grading and survival were appraised in samples from TCGA dataset and BLCA tissue microarray. Colony formation assays and CC...