Gong Xiaoxia, Li Ning, Sun Chen, Li Zhaoshui, Xie Hao
School of Life Science and Technology, MOE Key Laboratory of Developmental Genes and Human Diseases, Southeast University, Nanjing, China.
Cardiovascular Department, Qingdao Hiser Hospital Affiliated to Qingdao University, Qingdao, China.
Front Pharmacol. 2022 May 4;13:874780. doi: 10.3389/fphar.2022.874780. eCollection 2022.
TEA domain transcription factor 4 (TEAD4) is a member of the transcriptional enhancer factor (TEF) family of transcription factors, which is studied to be linked to the tumorigenesis and progression of various forms of cancers, including lung adenocarcinoma (LUAD). However, the specific function of this gene in the progression of LUAD remains to be explored. A total of 19 genes related to the Hippo pathway were analyzed to identify the significant genes involved in LUAD progression. The TCGA-LUAD data (n = 585) from public databases were mined, and the differentially expressed genes (DEGs) in patients with the differential level of were identified. The univariate Cox regression, zero LASSO regression coefficients, and multivariate Cox regression were performed to identify the independent prognostic signatures. The immune microenvironment estimation in the two subgroups, including immune cell infiltration, HLA family genes, and immune checkpoint genes, was assessed. The Gene Set Enrichment Analysis (GSEA) and GO were conducted to analyze the functional enrichment of DEGs between the two risk groups. The potential drugs for the high-risk subtypes were forecasted the mode of action (moa) module of the connectivity map (CMap) database. was found to be significantly correlated with poor prognosis in LUAD-patients. A total of 102 DEGs in -high vs. -low groups were identified. Among these DEGs, four genes (, , , and ) were identified as the independent prognostic signature to conduct the Cox risk model. The immune microenvironment estimation indicated a strong relationship between the high expression and immunotherapeutic resistance. The GSEA and GO showed that pathways, including cell cycle regulation, were enriched in the high-risk group, while immune response-related and metabolism biological processes were enriched in the low-risk group. Several small molecular perturbagens targeting or , by the mode of action (moa) modules of the glucocorticoid receptor agonist, cyclooxygenase inhibitor, and NFkB pathway inhibitor, were predicted to be suited for the high-risk subtypes based on the high expression. The current study revealed is an immune regulation-related predictor of prognosis and a novel therapeutic target for LUAD.
TEA结构域转录因子4（TEAD4）是转录增强因子（TEF）家族转录因子的成员，研究表明其与包括肺腺癌（LUAD）在内的多种癌症的发生和发展有关。然而，该基因在LUAD进展中的具体功能仍有待探索。分析了总共19个与Hippo通路相关的基因，以确定参与LUAD进展的重要基因。挖掘了来自公共数据库的TCGA-LUAD数据（n = 585），并确定了不同水平患者中的差异表达基因（DEG）。进行单变量Cox回归、零LASSO回归系数和多变量Cox回归以确定独立的预后特征。评估了两个亚组中的免疫微环境，包括免疫细胞浸润、HLA家族基因和免疫检查点基因。进行基因集富集分析（GSEA）和GO分析以分析两个风险组之间DEG的功能富集。通过连接图谱（CMap）数据库的作用模式（moa）模块预测了高危亚型的潜在药物。发现其与LUAD患者的不良预后显著相关。在高与低组中总共鉴定出102个DEG。在这些DEG中，四个基因（，，和）被鉴定为独立的预后特征以构建Cox风险模型。免疫微环境评估表明高表达与免疫治疗耐药性之间存在密切关系。GSEA和GO表明，包括细胞周期调节在内的通路在高危组中富集，而免疫反应相关和代谢生物学过程在低危组中富集。基于高表达，通过糖皮质激素受体激动剂、环氧化酶抑制剂和NFkB通路抑制剂的作用模式（moa）模块预测，几种靶向或的小分子干扰剂适用于高危亚型。当前研究表明是LUAD的免疫调节相关预后预测因子和新的治疗靶点。
