Department of Urology, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao, 266000, China.
Key Laboratory, Department of Urology and Andrology, The Affiliated Hospital of Qingdao University, Qingdao, China.
BMC Cancer. 2021 Apr 24;21(1):458. doi: 10.1186/s12885-021-08229-1.
Bladder cancer (BLCA) is a common malignant tumor of urinary system with high morbidity and mortality. In recent years, immunotherapy has played a significant role in the treatment of BLCA. Tumor mutation burden (TMB) has been reported to be a powerful biomarker for predicting tumor prognosis and efficacy of immunotherapy. Our study aimed to explore the relationship between TMB, prognosis and immune infiltration to identify the key genes in BLCA.
Clinical information, somatic mutation and gene expression data of BLCA patients were downloaded from The Cancer Genome Atlas (TCGA) database. Patients were divided into high and low TMB groups according to their calculated TMB scores. Gene Set Enrichment Analysis (GSEA) was performed to screen for significantly enriched pathways. Differentially expressed genes (DEGs) between the two groups were identified. Univariate Cox analysis and Kaplan-Meier survival analysis were applied for screening key genes. Immune infiltration was performed for TMB groups and NTRK3.
Higher TMB scores were related with poor survival in BLCA. After filtering, 36 DEGs were identified. NTRK3 had the highest hazard ratio and significant prognostic value. Co-expressed genes of NTRK3 were mainly involved in several pathways, including DNA replication, basal transcription factors, complement and coagulation cascades, and ribosome biogenesis in eukaryotes. There was a significant correlation among TMB scores, NTRK3 expression and immune infiltration.
Our results suggest that NTRK3 is a TMB-related prognostic biomarker, which lays the foundation for further research on the immunomodulatory effect of NTRK3 in BLCA.
膀胱癌(BLCA)是一种常见的泌尿系统恶性肿瘤,发病率和死亡率均较高。近年来,免疫疗法在 BLCA 的治疗中发挥了重要作用。肿瘤突变负担(TMB)已被报道为预测肿瘤预后和免疫治疗疗效的有力生物标志物。本研究旨在探讨 TMB 与预后和免疫浸润的关系,以确定 BLCA 的关键基因。
从癌症基因组图谱(TCGA)数据库中下载 BLCA 患者的临床信息、体细胞突变和基因表达数据。根据计算的 TMB 评分将患者分为高 TMB 组和低 TMB 组。进行基因集富集分析(GSEA)以筛选显著富集的途径。鉴定两组间差异表达基因(DEGs)。应用单因素 Cox 分析和 Kaplan-Meier 生存分析筛选关键基因。对 TMB 组和 NTRK3 进行免疫浸润分析。
较高的 TMB 评分与 BLCA 的不良预后相关。经过筛选,鉴定出 36 个 DEGs。NTRK3 的风险比最高且具有显著的预后价值。NTRK3 的共表达基因主要参与几种途径,包括 DNA 复制、基础转录因子、补体和凝血级联、真核生物核糖体生物发生。TMB 评分、NTRK3 表达与免疫浸润之间存在显著相关性。
我们的研究结果表明,NTRK3 是一个与 TMB 相关的预后生物标志物,为进一步研究 NTRK3 在 BLCA 中的免疫调节作用奠定了基础。