胶质瘤是最常见的颅内恶性肿瘤。免疫渗透和肿瘤干细胞与胶质瘤的预后相关。虽然富含寡脂激酶结构域家族A 4（PLEKHA4）在各种人类癌症中广泛表达，但其在胶质瘤中的作用尚不清楚。我们通过分析中国胶质瘤基因组图谱（CGGA）和癌症基因组图谱（TCGA）数据库中的相关数据，研究了PLEKHA4在胶质瘤中的特征和临床意义。使用基因集富集分析（GSEA）确定PLEKHA4在胶质瘤中可能涉及的功能和通路。使用从表观遗传学和转录组学特征计算的干细胞性评分（ss）分析了PLEKHA4表达与致癌去分化程度之间的关系。我们还使用CIBERSORT数据库探索了PLEKHA4表达与胶质瘤中免疫细胞浸润的关系。此外，还使用GDSC和GTRP数据库的数据集进行了药物敏感性分析。此外，我们还进行了相关的体外实验研究。PLEKHA4 DNA低甲基化状态与其在胶质瘤组织中的高表达以及不良预后相关。单变量和多变量Cox分析表明，PLEKHA4表达可能作为胶质瘤患者的独立预后因子。GSEA表明，高PLEKHA4表达与JAK / STAT、Wnt、JNK信号通路有关，并参与了细胞凋亡、细胞骨架和细胞粘附等生物过程。此外，PLEKHA4表达增加与更高的胶质瘤干细胞性评分相关，而PLEKHA4表达水平较低则较低。此外，PLEKHA4的表达与胶质瘤CD4+ T细胞、B细胞、中性粒细胞、巨噬细胞和树突细胞的浸润有关。药物敏感性分析还显示，PLEKHA4表达与几种小分子激酶抑制剂的敏感性呈负相关。此外，体外实验证实，PLEKHA4沉默抑制了胶质瘤细胞的增殖。PLEKHA4在胶质瘤组织中高表达，并与肿瘤干细胞性、免疫细胞浸润和增殖相关，提示其可能作为胶质瘤的新型预后生物标志物和治疗靶点。© 2023 IMR Press发表的作者。

Glioma is the most common intracranial malignancy. Immune-infiltration and tumour stemness are associated with the prognosis of glioma. Although pleckstrin homology containing family A, number 4 (PLEKHA4) is widely expressed in various human cancers, its role in glioma remains unclear.We examined the features and clinical significance of PLEKHA4 in gliomas by analysing relevant data from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. Gene set enrichment analysis (GSEA) was performed to determine the possible functions and pathways involving PLEKHA4 in glioma. The relationship between PLEKHA4 expression and the degree of oncogenic dedifferentiation was analysed using stemness scores (ss) calculated from epigenetic and transcriptomic features. We also explored the relationship between PLEKHA4 expression and immune cell infiltration in gliomas using the CIBERSORT databases. Furthermore, drug sensitivity analysis was performed using datasets from the GDSC and GTRP databases. In addition, we performed relevant in vitro experimental studies.PLEKHA4 DNA hypomethylation status was associated with its high expression in glioma tissues as well as poor prognoses. Univariate and multivariate Cox analyses indicated that PLEKHA4 expression may be considered as an independent prognostic factor in patients with glioma. GSEA indicated that high PLEKHA4 expression was associated with Janus kinase (JAK)/signal transducer and activator of transcription (STAT), Wingless-Type MMTV Integration Site Family (Wnt), JUN N-terminal kinase (JNK) signalling pathways and involved in apoptotic, cytoskeletal, and cell adhesion biological processes (BPs). In addition, increased PLEKHA4 expression was associated with higher glioma stemness scores than lower PLEKHA4 expression levels. Furthermore, the expression of PLEKHA4 was shown to be associated with glioma infiltration by CD4+ T cells, B cells, neutrophils, macrophages, and dendritic cells. Drug sensitivity analysis also showed that PLEKHA4 expression was negatively correlated with the sensitivity of several small molecule kinase inhibitors. Furthermore, in vitro experiments confirmed that PLEKHA4 knockdown inhibited the proliferation of glioma cells.PLEKHA4 is highly expressed in glioma tissues and correlated with tumour stemness, immune cell infiltration and proliferation, suggesting its potential as a novel prognostic biomarker and therapeutic target in glioma.© 2023 The Author(s). Published by IMR Press.