Li Lin, Bai Long, Lin Huan, Dong Lin, Zhang Rumeng, Cheng Xiao, Liu Zexian, Ouyang Yi, Ding Keshuo
Department of Pathology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, China.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Comput Struct Biotechnol J. 2021 Oct 12;19:5637-5646. doi: 10.1016/j.csbj.2021.10.013. eCollection 2021.
Whether tumor mutational burden (TMB) is related to improved survival outcomes or the promotion of immunotherapy in various malignant tumors remains controversial, and we lack a comprehensive understanding of TMB across cancers. Based on the data obtained from The Cancer Genome Atlas (TCGA), we conducted a multiomics analysis of TMB across 21 cancer types to identify characteristics related to TMB and determine the mechanism as it relates to prognosis, gene expression, gene mutation and signaling pathways. In our study, TMB was found to have a significant relationship with prognosis for 21 tumors, and the relationship was different in different tumors. TMB may also be related to different outcomes for patients with different tumor subtypes. TMB was confirmed to be correlated with clinical information, such as age and sex. Mutations in and in beast invasive carcinoma (BRCA), in colon adenocarcinoma (COAD), in esophageal carcinoma (ESCA), and in brain lower grade glioma (LGG), in stomach adenocarcinoma (STAD), and in uterine corpus endometrial carcinoma (UCEC) were demonstrated to be correlated with lower TMB. Moreover, we identified differentially expressed genes (DEGs) and differentially methylated regions (DMRs) according to different TMB levels in 21 cancers. We also investigated the correlation between enrichment of signaling pathways, immune cell infiltration and TMB. In conclusion, we identified multiomic characteristics related to the TMB in 21 tumors, providing support for a comprehensive understanding of the role of TMB in different tumors.
肿瘤突变负荷（TMB）是否与各种恶性肿瘤的生存结果改善或免疫治疗的促进相关仍存在争议，并且我们对跨癌症的TMB缺乏全面的了解。基于从癌症基因组图谱（TCGA）获得的数据，我们对21种癌症类型的TMB进行了多组学分析，以识别与TMB相关的特征，并确定其与预后、基因表达、基因突变和信号通路相关的机制。在我们的研究中，发现TMB与21种肿瘤的预后有显著关系，并且这种关系在不同肿瘤中有所不同。TMB也可能与不同肿瘤亚型患者的不同结果相关。TMB被证实与年龄和性别等临床信息相关。在乳腺浸润性癌（BRCA）中的 和 突变、结肠腺癌（COAD）中的 突变、食管癌（ESCA）中的 突变、低级别脑胶质瘤（LGG）中的 和 突变、胃腺癌（STAD）中的 突变以及子宫内膜癌（UCEC）中的 突变被证明与较低的TMB相关。此外，我们根据21种癌症中不同的TMB水平鉴定了差异表达基因（DEG）和差异甲基化区域（DMR）。我们还研究了信号通路富集、免疫细胞浸润与TMB之间的相关性。总之，我们鉴定了21种肿瘤中与TMB相关的多组学特征，为全面了解TMB在不同肿瘤中的作用提供了支持。
