Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China.
Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China.
Aging (Albany NY). 2020 Mar 12;12(5):4603-4616. doi: 10.18632/aging.102917.
Growing evidence highlighted the tumor mutational burden (TMB) as an important feature of carcinogenesis and therapeutic efficacy in esophageal cancer (EC). Our study aimed to explore the genomic landscape and the correlation between TMB and immune cell infiltration in EC patients with or without radiotherapy. The EC patients were categorized into high TMB (TMB-H) and low TMB (TMB-L) groups by the ESTIMATE algorithm, and subgroup analysis was performed based on receiving radiotherapy or not. Univariate regression analysis indicated TMB and TNM stages as high-risk prognostic factors (Hazard ratio > 1 and P < 0.05). Multivariate regression analysis suggested TMB as an independent prognostic factor (Hazard ratio = 1.051, P = 0.003). Kaplan-Meier analysis showed no significant difference of the overall survival (OS) between TMB-H and TMB-L groups (P = 0.082). However, EC patients without radiotherapy in the TMB-H group had significantly decreased OS (P = 0.038) and increased Tregs cell infiltration (P = 0.033). These results suggested TMB as a prognostic marker for EC patients. Especially for patients who did not receive radiotherapy, the prognosis of TMB-H patients was significantly poorer than that of TMB-L patients, which might result from the different regulatory T cell infiltration.
越来越多的证据强调了肿瘤突变负担(TMB)作为食管癌(EC)发生和治疗效果的一个重要特征。我们的研究旨在探索伴有或不伴有放疗的 EC 患者的基因组图谱以及 TMB 与免疫细胞浸润之间的相关性。我们通过 ESTIMATE 算法将 EC 患者分为高 TMB(TMB-H)和低 TMB(TMB-L)组,并进行了基于是否接受放疗的亚组分析。单因素回归分析表明 TMB 和 TNM 分期是高风险的预后因素(风险比>1,P<0.05)。多因素回归分析表明 TMB 是独立的预后因素(风险比=1.051,P=0.003)。Kaplan-Meier 分析显示 TMB-H 组和 TMB-L 组之间总生存期(OS)无显著差异(P=0.082)。然而,在 TMB-H 组中未接受放疗的 EC 患者的 OS 显著降低(P=0.038),调节性 T 细胞浸润增加(P=0.033)。这些结果表明 TMB 是 EC 患者的预后标志物。特别是对于未接受放疗的患者,TMB-H 患者的预后明显差于 TMB-L 患者,这可能是由于不同的调节性 T 细胞浸润所致。