Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, China.
Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, China.
Thorac Cancer. 2020 Mar;11(3):728-737. doi: 10.1111/1759-7714.13325. Epub 2020 Jan 28.
Local relapses and metastases are primary causes of death in lung cancer patients. In the present study, we aimed to develop a prognostic signature based on metastasis-associated lncRNAs in patients with lung adenocarcinoma (LUAD).
Firstly, the potential metastasis-associated lncRNAs were identified by analyzing high-throughput data from The Cancer Genome Atlas (TCGA), and based on which, an lncRNA signature was constructed for prediction of relapse in LUAD patients using Cox proportional hazards regression analysis. Moreover, the prognostic performance of the lncRNA signature was evaluated using Kaplan-Meier survival analysis, time-dependent receiver operating characteristic (ROC) curve and Cox analysis, respectively. In addition, the potential metastasis-associated function of these six lncRNAs was confirmed by lncRNA over-expression or depletion and in vitro transwell assays in LUAD cells.
An lncRNA signature consisting of six most important prognostic factors (LINC01819, ZNF649-AS1, HNF4A-AS1, FAM222A-AS1, LINC02323 and LINC00672) was developed. The signature was an independent predictor for patients' relapse-free survival (RFS), which could provide higher tumor relapse prediction capability compared with the TNM staging system at three years and five years, respectively (P = 0.0209 and P = 0.0468). Furthermore, the combination of this lncRNA signature and TNM stage had better prognostic value than TNM stage alone at three and five years, respectively (P = 0.0006 and P = 0.0096). Additionally, all the lncRNAs of the signature had a regulatory role in the LUAD cell mobility.
This novel six-lncRNA signature had considerable prognostic value for prediction of relapse in LUAD patients.
Significant findings of the study The unique metastasis-associated lncRNA signature was related to tumor metastasis and prognosis in LUAD patients. What this study adds This signature had considerable prognostic value for prediction of relapse in LUAD patients.
局部复发和转移是肺癌患者死亡的主要原因。本研究旨在基于肺癌腺癌（LUAD）患者的转移相关 lncRNA 构建一个预后标志物。
首先，通过分析癌症基因组图谱（TCGA）的高通量数据，确定了潜在的转移相关 lncRNA，并基于此，采用 Cox 比例风险回归分析构建用于预测 LUAD 患者复发的 lncRNA 标志物。此外，分别通过 Kaplan-Meier 生存分析、时间依赖性接受者操作特征（ROC）曲线和 Cox 分析评估 lncRNA 标志物的预后性能。此外，通过在 LUAD 细胞中进行 lncRNA 过表达或耗尽以及体外 transwell 实验，验证了这六个 lncRNA 的潜在转移相关功能。
构建了一个由六个最重要的预后因素（LINC01819、ZNF649-AS1、HNF4A-AS1、FAM222A-AS1、LINC02323 和 LINC00672）组成的 lncRNA 标志物。该标志物是患者无复发生存期（RFS）的独立预测因子，与 TNM 分期系统相比，在三年和五年时均能提供更高的肿瘤复发预测能力（P = 0.0209 和 P = 0.0468）。此外，该 lncRNA 标志物与 TNM 分期的组合在三年和五年时的预后价值均优于 TNM 分期（P = 0.0006 和 P = 0.0096）。此外，该标志物中的所有 lncRNA 均对 LUAD 细胞迁移具有调节作用。
该新型六 lncRNA 标志物对预测 LUAD 患者复发具有重要的预后价值。
