Zhang Xuezhong, Zhang Xuebin, Liu Tonggang, Sha Kaihui
Department of Laboratory Medicine, Zibo Central Hospital, Zibo, Shandong, China.
Department of Anorectal Surgery, Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, China.
Sci Rep. 2024 Aug 2;14(1):17875. doi: 10.1038/s41598-024-68784-y.
TNFAIP8 family molecules have been recognized for their involvement in the progression of tumors across a range of cancer types. Emerging experimental data suggests a role for certain TNFAIP8 family molecules in the development of glioma. Nonetheless, the comprehensive understanding of the genomic alterations, prognostic significance, and immunological profiles of TNFAIP8 family molecules in glioma remains incomplete. In the study, using the comprehensive bioinformatics tools, we explored the unique functions of 4 TNFAIP8 members including TNFAIP8, TNFAIP8L1, TNFAIP8L2 and TNFAIP8L3 in glioma. The expressions of TNFAIP8, TNFAIP8L1, TNFAIP8L2, and TNFAIP8L3 were notably upregulated in glioma tissues compared to normal tissues. Furthermore, survival analysis indicated that elevated expression levels of TNFAIP8, TNFAIP8L1 and TNFAIP8L2 were correlated with unfavorable outcomes in terms of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) among glioma patients. Genetic modifications, such as mutations and copy number alterations, within the TNFAIP8 family exhibited a significant association with extended OS, DSS and PFS in individuals diagnosed with glioma. The findings suggest a noteworthy correlation between TNFAIP8 family members and the age and 1p/19q codeletion status of glioma patients. We also found that there were significant relationships between TNFAIP8 family expression and tumor immunity in glioma. Furthermore, functional annotation of TNFAIP8 family members and their co-expressed genes in gliomas was carried out using GO and KEGG pathway analysis. The GO analysis revealed that the primary biological processes influenced by the TNFAIP8 family co-expressed genes included cell chemotaxis, temperature homeostasis, and endocytic vesicle formation. Additionally, the KEGG analysis demonstrated that TNFAIP8 family co-expressed genes are involved in regulating various pathways such as inflammatory mediator regulation of TRP channels, pathways in cancer, prolactin signaling pathway, and Fc gamma R-mediated phagocytosis. Overall, the findings suggest that TNFAIP8 family members may play a significant role in the development of glioma and have the potential to serve as prognostic indicators and therapeutic targets for individuals with glioma.
TNFAIP8家族分子因其在多种癌症类型的肿瘤进展中所起的作用而受到关注。新出现的实验数据表明，某些TNFAIP8家族分子在胶质瘤的发生发展中发挥作用。尽管如此，对TNFAIP8家族分子在胶质瘤中的基因组改变、预后意义和免疫特征的全面了解仍不完整。在本研究中，我们使用综合生物信息学工具，探索了TNFAIP8、TNFAIP8L1、TNFAIP8L2和TNFAIP8L3这4个TNFAIP8成员在胶质瘤中的独特功能。与正常组织相比，TNFAIP8、TNFAIP8L1、TNFAIP8L2和TNFAIP8L3在胶质瘤组织中的表达显著上调。此外，生存分析表明，TNFAIP8、TNFAIP8L1和TNFAIP8L2表达水平升高与胶质瘤患者的总生存期（OS）、疾病特异性生存期（DSS）和无进展生存期（PFI）的不良预后相关。TNFAIP8家族内的基因修饰，如突变和拷贝数改变，在诊断为胶质瘤的个体中与延长的OS、DSS和PFS显著相关。研究结果表明，TNFAIP8家族成员与胶质瘤患者的年龄和1p/19q共缺失状态之间存在显著相关性。我们还发现，TNFAIP8家族表达与胶质瘤中的肿瘤免疫之间存在显著关系。此外，使用GO和KEGG通路分析对TNFAIP8家族成员及其在胶质瘤中共表达的基因进行了功能注释。GO分析显示，受TNFAIP8家族共表达基因影响的主要生物学过程包括细胞趋化性、体温稳态和内吞囊泡形成。此外，KEGG分析表明，TNFAIP8家族共表达基因参与调节多种通路，如TRP通道的炎症介质调节、癌症通路、催乳素信号通路和FcγR介导的吞噬作用。总体而言，研究结果表明，TNFAIP8家族成员可能在胶质瘤的发生发展中发挥重要作用，并有潜力作为胶质瘤患者的预后指标和治疗靶点。
