Department of Stomatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Front Immunol. 2024 Oct 17;15:1484226. doi: 10.3389/fimmu.2024.1484226. eCollection 2024.
The aberrant expression of AEG-1 is significantly correlated with tumorigenesis, development, neurodegeneration and inflammation. However, the relationship between AEG-1 expression and immune infiltration in OSCC, as well as other tumor types, has yet to be comprehensively analyzed.
The expression levels, prognostic and clinicopathological characteristics, mutation patterns and methylation landscapes of AEG-1 in various tumors were obtained from multiple databases, including TIMER, GEPIA, HPA, TCGA, UALCAN, cBioPortal, SMART and TISIDB, in addition to single-cell RNA-seq data. The integration of these datasets facilitated the elucidation of the relationships among pan-cancer cellular heterogeneity, immune infiltration and AEG-1 expression levels. experiments created AEG-1 overexpressing cell lines, and mRNA-seq analyzed AEG-1-related differential genes in OSCC. RT-PCR validated these findings using xenograft tumors. Tumor cell lines were developed to study AEG-1's effects through H&E, Masson, and PAS staining. Immunohistochemistry examined AEG-1-related gene expression patterns.
Our analysis demonstrated that AEG-1 is highly expressed across various cancer types and is associated with tumor grade and patient prognosis. Additionally, AEG-1 amplification was observed in multiple cancers. Notably, we identified a significant elevation of AEG-1 expression in OSCC, which strongly correlated with patient prognosis and immune infiltration. Through mRNA-seq analysis of differentially expressed genes and immune-related gene sets, we identified a strong correlation between AEG-1 and immune infiltration markers such as LCP2, CD247, HLA-DPA1, HLA-DRA, HLA-DRB1, CIITA and CD74 in OSCC. Additionally, AEG-1 was found to regulate Th1/Th2 immune homeostasis, promote glycogen accumulation, and contribute to tumor fibrosis.
In conclusion, AEG-1 significantly correlates with prognosis and immune infiltration across various cancer types and holds potential as a novel prognostic immune biomarker for OSCC. This finding may facilitate the identification of patients who are most likely to benefit from adjuvant immunotherapy.
AEG-1 的异常表达与肿瘤发生、发展、神经退行性变和炎症显著相关。然而，AEG-1 表达与 OSCC 及其他肿瘤类型中免疫浸润的关系尚未得到全面分析。
从多个数据库（包括 TIMER、GEPIA、HPA、TCGA、UALCAN、cBioPortal、SMART 和 TISIDB）以及单细胞 RNA-seq 数据中获取了 AEG-1 在各种肿瘤中的表达水平、预后和临床病理特征、突变模式和甲基化图谱。整合这些数据集有助于阐明泛癌细胞异质性、免疫浸润和 AEG-1 表达水平之间的关系。通过构建 AEG-1 过表达细胞系，并进行 OSCC 的 mRNA-seq 分析，以确定 AEG-1 相关的差异基因。利用异种移植瘤的 RT-PCR 验证了这些发现。通过 H&E、Masson 和 PAS 染色研究肿瘤细胞系中 AEG-1 的作用。免疫组化检测 AEG-1 相关基因的表达模式。
我们的分析表明，AEG-1 在多种癌症类型中高表达，与肿瘤分级和患者预后相关。此外，在多种癌症中观察到 AEG-1 扩增。值得注意的是，我们发现 OSCC 中 AEG-1 表达显著升高，与患者预后和免疫浸润密切相关。通过 OSCC 中差异表达基因和免疫相关基因集的 mRNA-seq 分析，我们发现 AEG-1 与免疫浸润标志物（如 LCP2、CD247、HLA-DPA1、HLA-DRA、HLA-DRB1、CIITA 和 CD74）之间存在很强的相关性。此外，我们发现 AEG-1 可调节 Th1/Th2 免疫稳态，促进糖原积累，并促进肿瘤纤维化。
总之，AEG-1 在多种癌症类型中与预后和免疫浸润显著相关，有望成为 OSCC 的新型预后免疫生物标志物。这一发现可能有助于识别最有可能从辅助免疫治疗中获益的患者。
