Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Department of Thoracic Surgery, Klinikum Ernst von Bergmann, Academic Hospital of Charité - Universitätsmedizin Berlin, Potsdam, Germany.
Thorac Cancer. 2021 Jul;12(13):1995-2006. doi: 10.1111/1759-7714.14002. Epub 2021 May 25.
Thymic epithelial tumors (TETs) are relatively rare malignant thoracic tumors. Tumor mutation burden (TMB) and immune infiltration play important roles in tumorigenesis.
Research data was obtained using the Cancer Genome Atlas (TCGA) database to evaluate the landscape of tumor mutations, related factors, and relationship of prognosis. The CIBERSORT algorithm was used to evaluate immune cell infiltration in TETs and its relationship with TMB. Immune-related differentially expressed genes (irDEGs) were identified. Hub irDEGs independently related to prognosis were analyzed using univariate and multivariate Cox proportional hazard models. A survival signature was constructed from hub irDEGs.
A total of 122 patients were included in this study. GTF2I was the most common gene mutation. Higher TMB was significantly associated with the later stage, more advanced pathological type, and older age. The overall survival (OS) of patients in the low-TMB group was significantly better. There was no significant correlation between TMB levels and PD-L1 expression. Enrichment analysis showed that DEGs were mainly involved in the P13K-Akt signaling pathway. There were significant differences in macrophage and other types of immune cell infiltration between the high- and low-TMB groups. CCR5, FASLG, and CD79A independently relating to prognosis were screened from 391 irDEGs. The low-risk group had a significantly better prognosis than the high-risk group based on the signature, which has a good predictive effect on OS.
In this study, TETs patients with high TMB had a significantly poor prognosis and an immune-related gene signature was found to effectively evaluate the long-term prognosis.
胸腺瘤（TETs）是一种相对罕见的恶性胸部肿瘤。肿瘤突变负担（TMB）和免疫浸润在肿瘤发生中起重要作用。
使用癌症基因组图谱（TCGA）数据库获取研究数据，以评估肿瘤突变、相关因素的景观，并分析其与预后的关系。使用 CIBERSORT 算法评估 TETs 中的免疫细胞浸润及其与 TMB 的关系。识别免疫相关差异表达基因（irDEGs）。使用单变量和多变量 Cox 比例风险模型分析与预后独立相关的枢纽 irDEGs。从枢纽 irDEGs 构建生存特征。
本研究共纳入 122 例患者。GTF2I 是最常见的基因突变。较高的 TMB 与晚期、更高级别的病理类型和更大年龄显著相关。低 TMB 组患者的总生存率（OS）显著更好。TMB 水平与 PD-L1 表达之间无显著相关性。富集分析表明，DEGs 主要参与 P13K-Akt 信号通路。高、低 TMB 组之间巨噬细胞和其他类型免疫细胞浸润存在显著差异。从 391 个 irDEGs 中筛选出与预后独立相关的 CCR5、FASLG 和 CD79A。基于该特征，低风险组的预后明显优于高风险组，对 OS 具有良好的预测效果。
在本研究中，TMB 较高的 TETs 患者预后明显较差，发现了一个与免疫相关的基因特征，可有效评估长期预后。
