Feng Yueyi, Feng Qingting, Xu Lingkai, Jiang Yiqing, Meng Fang, Shu Xiaochen
Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou 215123, China.
Department of General Surgery, Harrison International Peace Hospital, Hengshui 053000, China.
J Oncol. 2019 Dec 6;2019:2654296. doi: 10.1155/2019/2654296. eCollection 2019.
Muscle-invasive bladder urothelial carcinoma (MIBC) is characteristic of high mortality and high recurrence. Distinguishing the prognostic risk of MIBC at the molecular level of miRNA expression is rarely performed and thus of great significance for the management and treatment of MIBC in clinics. Adaptive lasso Cox's proportional hazards model was used to explore the relationship between differential expression miRNAs (DEmiRNAs) and MIBC survival. Furthermore, we evaluated the epithelial-mesenchymal transition (EMT) score and immune infiltration abundance by exploring EMT signature genes and TIMER database, respectively. A total of 8 DEmiRNAs were detected to be associated with the survival rate of MIBC by using the lasso Cox algorithm. Through the linear combination of these 8 DEmiRNAs, we constructed a calculated marker, which could be used to distinguish the prognosis risk in both TCGA dataset (HR = 2.03, 95% CI = (1.47, 2.83)) and independent validation dataset (HR = 7.74, 95% CI = (1.05, 56.93)). Meanwhile, the constructed marker had reasonably high predictive values of the AUC (area under the curve) in the TCGA dataset and validation dataset being 0.73 and 0.63, respectively. In addition, we observed that the expression values of let-7c, miR-100, and miR-145 were associated with EMT score and the abundance of macrophage in tumor tissue as well. This newly identified risk score signature based on the combination of 8 miRNAs could significantly predict the prognostic risk of MIBC and might provide insight into immunotherapy and targeted therapy of MIBC.
肌层浸润性膀胱尿路上皮癌（MIBC）具有高死亡率和高复发率的特点。在miRNA表达的分子水平上区分MIBC的预后风险的研究很少，因此对临床中MIBC的管理和治疗具有重要意义。采用自适应套索Cox比例风险模型探讨差异表达miRNA（DEmiRNA）与MIBC生存之间的关系。此外，我们分别通过探索EMT特征基因和TIMER数据库来评估上皮-间质转化（EMT）评分和免疫浸润丰度。使用套索Cox算法共检测到8种DEmiRNA与MIBC的生存率相关。通过这8种DEmiRNA的线性组合，我们构建了一个计算标记，可用于区分TCGA数据集（HR = 2.03，95%CI =（1.47，2.83））和独立验证数据集（HR = 7.74，95%CI =（1.05，56.93））中的预后风险。同时，构建的标记在TCGA数据集和验证数据集中的AUC（曲线下面积）预测值相当高，分别为0.73和0.63。此外，我们观察到let-7c、miR-100和miR-145的表达值也与肿瘤组织中的EMT评分和巨噬细胞丰度相关。这种基于8种miRNA组合新鉴定的风险评分特征可以显著预测MIBC的预后风险，并可能为MIBC的免疫治疗和靶向治疗提供思路。
