Department of Thoracic Surgery, Ruijin Hospital; Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Thoracic Surgery, Ruijin Hospital; Shanghai Jiao Tong University School of Medicine, Shanghai, China
Ann Clin Lab Sci. 2021 Jan;51(1):44-54.
The question of whether the tumor mutation burden (TMB) is associated with either improved survival outcomes or improvement of immunotherapies remains controversial in various malignancies. The aim of this study is to investigate the genomic landscape of the relationship between TMB and immune cell infiltration in thymic epithelial tumors (TETs).
We downloaded somatic mutation data, transcriptome sequencing data, and clinical information of TETs from the Cancer Genome Atlas (TCGA) database. We assessed the abundance of 22 immune fractions between low-TMB (TMB-L) and high-TMB (TMB-H) groups using the "CIBERSORT" package.
Missense mutation had the highest frequency of mutation among the nine variant classifications in TETs. Higher TMB levels were associated with poor survival outcomes (<0.05), and higher Masaoka stages (<0.05). More importantly, TMB levels were much higher in the thymic cancer than in thymoma (<0.01). The infiltration levers of naive CD4(+) T cells and regulatory T cells were significantly higher in the TMB-L group than in the TMB-H group, and this was further associated with better overall survival (OS) in patients with TETs.
The present study indicates that the prognosis of TMB-H patients with TETs is significantly poorer than is that of TMB-L patients, which might result from the different levels of infiltration of naive CD4(+) T cells and regulatory T cells.
肿瘤突变负担（TMB）与生存结局改善或免疫治疗改善之间的关系在各种恶性肿瘤中仍存在争议。本研究旨在探讨 TMB 与胸腺癌（TET）免疫细胞浸润之间关系的基因组特征。
我们从癌症基因组图谱（TCGA）数据库中下载了 TET 的体细胞突变数据、转录组测序数据和临床信息。我们使用“CIBERSORT”程序包评估了低 TMB（TMB-L）和高 TMB（TMB-H）组之间 22 种免疫细胞分数的丰度。
错义突变是 TET 中九个变异分类中突变频率最高的。较高的 TMB 水平与不良生存结局相关（<0.05），Masaoka 分期较高（<0.05）。更重要的是，胸腺癌的 TMB 水平明显高于胸腺瘤（<0.01）。TMB-L 组的幼稚 CD4+T 细胞和调节性 T 细胞浸润水平明显高于 TMB-H 组，这与 TET 患者的总体生存（OS）更好相关。
本研究表明，TET 中 TMB-H 患者的预后明显差于 TMB-L 患者，这可能是由于幼稚 CD4+T 细胞和调节性 T 细胞浸润水平的不同所致。
