Henan Provincial Engineering Laboratory of Insects Bio-reactor, Nanyang Normal University, Nanyang, Henan, China.
The Department of Science and Technology, Zhengzhou Revogene Ltd, Zhengzhou, Henan, China.
Front Immunol. 2023 Sep 21;14:1242972. doi: 10.3389/fimmu.2023.1242972. eCollection 2023.
It is now understood that APOBEC3 family proteins (A3s) are essential in tumor progression, yet their involvement in tumor immunity and stemness across diverse cancer types remains poorly understood.
In the present study, comprehensive genome-wide statistical and bioinformatic analyses were conducted to elucidate A3 family expression patterns, establishing clinically relevant correlations with prognosis, the tumor microenvironment(TME), immune infiltration, checkpoint blockade, and stemness across cancers. Different experimental techniques were applied, including RT-qPCR, immunohistochemistry, sphere formation assays, Transwell migration assays, and wound-healing assays, to investigate the impact of A3C on low-grade glioma (LGG) and glioblastoma multiforme (GBM), as well as its function in glioma stem cells(GSCs).
Dysregulated expression of A3s was observed in various human cancer tissues. The prognostic value of A3 expression differed across cancer types, with a link to particularly unfavorable outcomes in gliomas. A3s are associated with the the TME and stemness in multiple cancers. Additionally, we developed an independent prognostic model based on A3s expression, which may be an independent prognostic factor for OS in patients with glioma. Subsequent validation underscored a strong association between elevated A3C expression and adverse prognostic outcomes, higher tumor grades, and unfavorable histology in glioma. A potential connection between A3C and glioma progression was established. Notably, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses implicated A3C in immune system-related diseases, with heightened A3C levels contributing to an immunosuppressive tumor microenvironment (TME) in glioma. Furthermore, experiments substantiated the role of A3C in sustaining and renewing glioma stem cells, as A3C deletion led to diminished proliferation, invasion, and migration of glioma cells.
The A3 family exhibits heterogeneous expression across various cancer types, with its expression profile serving as a predictive marker for overall survival in glioma patients. A3C emerges as a regulator of glioma progression, exerting its influence through modulation of the tumor microenvironment and regulation of stemness.
现在人们已经了解到 APOBEC3 家族蛋白（A3s）在肿瘤进展中至关重要，但它们在不同癌症类型中的肿瘤免疫和干性中的作用仍知之甚少。
本研究进行了全面的全基因组统计和生物信息学分析，以阐明 A3 家族的表达模式，确定与预后、肿瘤微环境（TME）、免疫浸润、检查点阻断和癌症中干性相关的临床相关相关性。应用不同的实验技术，包括 RT-qPCR、免疫组织化学、球体形成测定、Transwell 迁移测定和划痕愈合测定，研究 A3C 对低级别神经胶质瘤（LGG）和胶质母细胞瘤（GBM）的影响及其在神经胶质瘤干细胞（GSCs）中的功能。
在各种人类癌症组织中观察到 A3s 的表达失调。A3 表达的预后价值因癌症类型而异，与神经胶质瘤的预后尤其不利有关。A3s 与多种癌症的 TME 和干性有关。此外，我们基于 A3s 表达开发了一个独立的预后模型，它可能是神经胶质瘤患者 OS 的独立预后因素。随后的验证强调了 A3C 表达升高与不良预后结局、更高的肿瘤分级和神经胶质瘤不良组织学之间的强烈关联。建立了 A3C 与神经胶质瘤进展之间的潜在联系。值得注意的是，基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析表明 A3C 与免疫系统相关疾病有关，神经胶质瘤中 A3C 水平升高导致免疫抑制性肿瘤微环境（TME）。此外，实验证实了 A3C 在维持和更新神经胶质瘤干细胞中的作用，因为 A3C 缺失导致神经胶质瘤细胞的增殖、侵袭和迁移减少。
A3 家族在各种癌症类型中表现出异质性表达，其表达谱可作为神经胶质瘤患者总生存的预测标志物。A3C 作为神经胶质瘤进展的调节剂，通过调节肿瘤微环境和调节干性发挥作用。
