Xu Hao-Qiang, Zhao Dan, Xu Shi-Hao, Mao Rui, Yang Wen-Qiong, Han Qi
Department of Neurology, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, 442008, Hubei, China.
Department of Neurology, Shenzhen Lansheng Brain Hospital, Shenzhen, 518109, China.
Sci Rep. 2025 Jul 11;15(1):25017. doi: 10.1038/s41598-025-08752-2.
Transmembrane (TMEM) proteins play a pivotal role in cancer progression, with TMEM150A specifically implicated in tumorigenesis. Despite its association with cancer, the precise role of TMEM150A in glioma remains underexplored. The expression of TMEM150A in glioma and its correlation with prognosis and the immune microenvironment were systematically analyzed. Prognostic models were developed using nomograms to establish the relationship between TMEM150A expression and patient survival. Bioinformatic analyses identified pathways and networks associated with TMEM150A co-expressed genes, while in vitro assays (CCK-8, migration, and invasion assays) examined the impact of TMEM150A inhibition on glioma cell proliferation and metastasis. TMEM150A was markedly overexpressed in glioma tissues and strongly associated with clinical features such as 1p/19q codeletion, age, IDH mutation status, histological subtype, WHO grade, and poor prognosis (P < 0.05). ROC analysis revealed high diagnostic accuracy, with area under the curve values of 0.962 and 0.896 for TCGA and XENA datasets, respectively, indicating the strong diagnostic potential of TMEM150A. Overexpression of TMEM150A was identified as a risk factor for poor prognosis. The constructed nomogram demonstrated that TMEM150A expression was predictive of survival, with time-dependent AUCs for 1, 3, and 5 years exceeding 0.75, confirming its prognostic relevance. TMEM150A co-expressed genes were linked to immune responses, necrotic cell death, antigen processing and presentation, cell differentiation, mast cell activation, endothelial cell migration, wound healing, and cell proliferation. Inhibition of TMEM150A expression suppressed U251 cell growth, migration, and invasion via epithelial-mesenchymal transition (EMT). Additionally, TMEM150A expression correlated with immune scores (r = 0.585), stromal scores (r = 0.498), ESTIMATE scores (r = 0.565), macrophage infiltration (r = 0.523), aDC (r = 0.473), and neutrophil presence (r = 0.453). Overexpression of TMEM150A serves as an independent prognostic marker in glioma and is intricately linked to the tumor's immune microenvironment. Targeting TMEM150A could inhibit glioma progression through EMT modulation, presenting a potential novel therapeutic avenue.
跨膜(TMEM)蛋白在癌症进展中起关键作用,其中TMEM150A特别涉及肿瘤发生。尽管其与癌症有关,但TMEM150A在胶质瘤中的精确作用仍未得到充分探索。系统分析了TMEM150A在胶质瘤中的表达及其与预后和免疫微环境的相关性。使用列线图开发预后模型,以建立TMEM150A表达与患者生存之间的关系。生物信息学分析确定了与TMEM150A共表达基因相关的途径和网络,而体外试验(CCK-8、迁移和侵袭试验)研究了TMEM150A抑制对胶质瘤细胞增殖和转移的影响。TMEM150A在胶质瘤组织中明显过表达,并与1p/19q共缺失、年龄、IDH突变状态、组织学亚型、WHO分级和预后不良等临床特征密切相关(P < 0.05)。ROC分析显示诊断准确性高,TCGA和XENA数据集的曲线下面积值分别为0.962和0.896,表明TMEM150A具有很强的诊断潜力。TMEM150A的过表达被确定为预后不良的危险因素。构建的列线图表明TMEM150A表达可预测生存,1年、3年和5年的时间依赖性AUC超过0.75,证实了其预后相关性。TMEM150A共表达基因与免疫反应、坏死性细胞死亡、抗原加工和呈递、细胞分化、肥大细胞活化、内皮细胞迁移、伤口愈合和细胞增殖有关。抑制TMEM150A表达可通过上皮-间质转化(EMT)抑制U251细胞的生长、迁移和侵袭。此外,TMEM150A表达与免疫评分(r = 0.585)、基质评分(r = 0.498)、ESTIMATE评分(r = 0.565)、巨噬细胞浸润(r = 0.523)、活化树突状细胞(r = 0.473)和中性粒细胞存在(r = 0.453)相关。TMEM150A的过表达是胶质瘤的独立预后标志物,并与肿瘤的免疫微环境密切相关。靶向TMEM150A可通过调节EMT抑制胶质瘤进展,提供了一条潜在的新治疗途径。