Han Ya-Lin, Chen Li, Wang Xu-Ning, Xu Mao-Lin, Qin Rui, Gong Fang-Ming, Sun Peng, Liu Hong-Yi, Teng Zhi-Peng, Li Zhao-Xia, Dai Guang-Hai
Department of General Surgery, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China.
Department of Oncology, PLA Rocket Force Characteristic Medical Centre, Beijing 100088, China.
Bioimpacts. 2024;14(6):30118. doi: 10.34172/bi.2024.30118. Epub 2024 Mar 2.
To explore the correlation between the tumour mutation burden (TMB) and prognosis and its clinical significance among patients with stage III gastric cancer (GC).
Patients with stage III GC were divided into a high TMB and low TMB group in both a study cohort of 38 patients and the Cancer Genome Atlas (TCGA) cohort of 173 patients. In the study cohort, next-generation sequencing was used to detect mutated GC genes and obtain TMB data. In the TCGA cohort, gene set enrichment analysis was performed, and the relationship between TMB, prognosis and clinicopathologic factors was analysed. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression levels of both proteins and genes. Cell viability was measured using methyl thiazolyl tetrazolium and transwell cell assays.
Patients in the high TMB group had better overall survival (OS) rates than patients in the low TMB group for both cohorts and TMB was associated with age, mutation signature 1 and mutation signature 17. The Cox regression analysis revealed that age, not TMB, was an independent prognosis factor. Furthermore, genes with high-frequency mutations were significantly enriched in the RTK-RAS and Notch signalling pathways. The activation of these pathways was lower in the high TMB compared with the low TMB group, and the proliferation and migration abilities of GC cells showed a similar pattern in both TMB groups.
Patients in the high TMB group had better OS rates than patients in the low TMB group. Genes with high-frequency mutations were significantly enriched in the RTK-RAS and Notch pathways. Hence, TMB could serve as a prognosis biomarker with potential clinical significance.
探讨Ⅲ期胃癌（GC）患者肿瘤突变负荷（TMB）与预后的相关性及其临床意义。
在一个由38例患者组成的研究队列和一个由173例患者组成的癌症基因组图谱（TCGA）队列中，将Ⅲ期GC患者分为高TMB组和低TMB组。在研究队列中，采用二代测序检测GC基因突变并获取TMB数据。在TCGA队列中，进行基因集富集分析，并分析TMB、预后与临床病理因素之间的关系。采用蛋白质免疫印迹法和定量实时聚合酶链反应检测蛋白质和基因的表达水平。使用甲基噻唑基四氮唑和Transwell细胞实验检测细胞活力。
在两个队列中，高TMB组患者的总生存率（OS）均高于低TMB组患者，且TMB与年龄、突变特征1和突变特征17相关。Cox回归分析显示，年龄而非TMB是独立的预后因素。此外，高频突变基因在RTK-RAS和Notch信号通路中显著富集。与低TMB组相比，高TMB组中这些信号通路的激活水平较低，且在两个TMB组中GC细胞的增殖和迁移能力表现出相似的模式。
高TMB组患者的OS率高于低TMB组患者。高频突变基因在RTK-RAS和Notch信号通路中显著富集。因此，TMB可作为具有潜在临床意义的预后生物标志物。
