背景:具有序列相似性的家族109,成员B(FAM109B)参与内吞运输并影响脑甲基化中的遗传变异。它是与免疫细胞相关疾病相关的重要基因之一。在肿瘤免疫系统中,甲基化可以调节肿瘤免疫,影响免疫细胞的成熟和功能反应。FAM109B是否参与肿瘤进展及其与肿瘤免疫微环境的相关性尚未公开。
方法:对FAM109B表达的全面泛癌分析,预后,豁免权,并进行了TMB。表达式,临床特征,使用TCGA评估FAM109B在低级别胶质瘤(LGG)中的预后价值,CGGA,和Gravendeel数据库。通过qRT-PCR验证FAM109B的表达,免疫组织化学(IHC),和蛋白质印迹(WB)。FAM109B与甲基化的关系,拷贝数变异(CNV),预后,免疫检查点(IC),并通过Cox回归分析探讨了LGG中常见的化疗药物敏感性,卡普兰-迈耶曲线,和Spearman相关分析。使用TIMER数据库和单细胞分析研究FAM109B水平及其分布。通过体外和体内实验进一步研究了FAM109B在神经胶质瘤中的潜在作用。
结果:FAM109B在各种肿瘤类型中显著升高,并与不良预后相关。其表达与低级别胶质瘤患者的侵袭性进展和不良预后有关。作为LGG的独立预后标志物。胶质瘤分级与FAM109B基因启动子甲基化呈负相关。免疫浸润和单细胞分析显示FAM109B在肿瘤相关巨噬细胞(TAMs)中的显著表达。FAM109B的表达与基因突变密切相关,免疫检查点(IC),和LGG中的化疗药物。体外研究显示LGG中FAM109B表达增加,与细胞增殖密切相关。体内研究显示sh-FAM109B组小鼠肿瘤生长较慢,更慢的减肥,更长的生存时间。
结论:FAM109B,作为低度胶质瘤的一种新的预后生物标志物,在TAM中表现出特异性过表达,可能是LGG患者的潜在治疗靶标。
BACKGROUND: Family with sequence similarity 109, member B (FAM109B) is involved in endocytic transport and affects genetic variation in brain methylation. It is one of the important genes related to immune cell-associated diseases. In the tumor immune system, methylation can regulate tumor immunity and influence the maturation and functional response of immune cells. Whether FAM109B is involved in tumor progression and its correlation with the tumor immune microenvironment has not yet been disclosed.
METHODS: A comprehensive pan-cancer analysis of FAM109B expression, prognosis, immunity, and TMB was conducted. The expression, clinical features, and prognostic value of FAM109B in low-grade gliomas (LGG) were evaluated using TCGA, CGGA, and Gravendeel databases. The expression of FAM109B was validated by qRT-PCR, immunohistochemistry (IHC), and Western blotting (WB). The relationship between FAM109B and methylation, Copy Number Variation (CNV), prognosis, immune checkpoints (ICs), and common chemotherapy drug sensitivity in LGG was explored through Cox regression, Kaplan-Meier curves, and Spearman correlation analysis. FAM109B levels and their distribution were studied using the TIMER database and single-cell analysis. The potential role of FAM109B in gliomas was further investigated through in vitro and in vivo experiments.
RESULTS: FAM109B was significantly elevated in various tumor types and was associated with poor prognosis. Its expression was related to aggressive progression and poor prognosis in low-grade glioma patients, serving as an independent prognostic marker for LGG. Glioma grade was negatively correlated with FAM109B DNA promoter methylation. Immune infiltration and single-cell analysis showed significant expression of FAM109B in tumor-associated macrophages (TAMs). The expression of FAM109B was closely related to gene mutations, immune checkpoints (ICs), and chemotherapy drugs in LGG. In vitro studies showed increased FAM109B expression in LGG, closely related to cell proliferation. In vivo studies showed that mice in the sh-FAM109B group had slower tumor growth, slower weight loss, and longer survival times.
CONCLUSIONS: FAM109B, as a novel prognostic biomarker for low-grade gliomas, exhibits specific overexpression in TAMs and may be a potential therapeutic target for LGG patients.