Liu Yu, Wang Liyu, Liu Hengchang, Li Chunxiang, He Jie
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Oncol. 2020 Feb 18;10:61. doi: 10.3389/fonc.2020.00061. eCollection 2020.
Metabolic syndrome (MetS) is associated with the development of esophageal squamous cell carcinoma (ESCC), and long non-coding RNAs (lncRNAs) are involved in a variety of mechanisms of MetS and tumor. This study will explore the prognostic effect of MetS and the associated lncRNA signature on ESCC. Our previous RNA-chip data (GSE53624, GSE53622) for 179 ESCC patients were reanalyzed according to MetS. The recurrence-free survival (RFS) was collected for these patients. The status of the MetS-related tumor microenvironment was analyzed with the CIBERSORT and ESTIMATE algorithms. A lncRNA signature was established with univariate and multivariate Cox proportional hazards regression (PHR) analysis and verified using the Kaplan-Meier survival curve analysis and time-dependent receiver operating characteristic (ROC) curves. A clinical predictive model was constructed based on multiple risk factors, evaluated using C-indexes and calibration curves, and verified using data from the GEO and TCGA databases. The results showed that MetS was an independent risk factor for ESCC patients conferring low OS and RFS. Tumor microenvironment analysis indicated that patients with MetS have high stromal scores and M2 macrophage infiltration. A six-lncRNA signature was established by 60 ESCC patients randomly selected from GSE53624 and identified with an effective predictive ability in validation cohorts (59 patients from GSE53624 and 60 patients from GSE53622), subgroup analysis, and ESCC patients from TCGA. MetS and the six-lncRNA signature could be regarded as independent risk factors and enhanced predictive ability in the clinical predictive model. Our results indicated that MetS was associated with poor prognosis in ESCC patients, and the possible mechanism was related to changes in the tumor microenvironment. MetS and the six-lncRNA signature could also serve as independent risk factors with available clinical application value.
代谢综合征（MetS）与食管鳞状细胞癌（ESCC）的发生发展相关，长链非编码RNA（lncRNAs）参与了MetS和肿瘤的多种机制。本研究将探讨MetS及相关lncRNA特征对ESCC的预后影响。我们根据MetS对之前179例ESCC患者的RNA芯片数据（GSE53624、GSE53622）进行了重新分析。收集这些患者的无复发生存期（RFS）。使用CIBERSORT和ESTIMATE算法分析MetS相关肿瘤微环境的状态。通过单因素和多因素Cox比例风险回归（PHR）分析建立lncRNA特征，并使用Kaplan-Meier生存曲线分析和时间依赖性受试者工作特征（ROC）曲线进行验证。基于多个风险因素构建临床预测模型，使用C指数和校准曲线进行评估，并使用来自GEO和TCGA数据库的数据进行验证。结果表明，MetS是ESCC患者低总生存期（OS）和RFS的独立危险因素。肿瘤微环境分析表明，MetS患者具有较高的基质评分和M2巨噬细胞浸润。从GSE53624中随机选择60例ESCC患者建立了一个六lncRNA特征，并在验证队列（来自GSE53624的59例患者和来自GSE53622的60例患者）、亚组分析以及来自TCGA的ESCC患者中确定其具有有效的预测能力。MetS和六lncRNA特征可被视为临床预测模型中的独立危险因素，并增强了预测能力。我们的结果表明，MetS与ESCC患者的不良预后相关，其可能机制与肿瘤微环境的变化有关。MetS和六lncRNA特征也可作为具有临床应用价值的独立危险因素。
