七长链非编码 RNA 标志物在食管鳞癌患者中的预后价值：长链非编码 RNA 表达分析。
The prognostic value of a seven-lncRNA signature in patients with esophageal squamous cell carcinoma: a lncRNA expression analysis.
机构信息
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Building 2, Room 704, Guzngzhou, 510060, China.
Guangdong Esophageal Cancer Institute, Guangzhou, 510060, China.
出版信息
J Transl Med. 2020 Jan 31;18(1):47. doi: 10.1186/s12967-020-02224-z.
BACKGROUND
Long non-coding RNAs (lncRNAs) have been reported to be prognostic biomarkers in many types of cancer. We aimed to identify a lncRNA signature that can predict the prognosis in patients with esophageal squamous cell carcinoma (ESCC).
METHODS
Using a custom microarray, we retrospectively analyzed lncRNA expression profiles in 141 samples of ESCC and 81 paired non-cancer specimens from Sun Yat-Sen University Cancer Center (Guangzhou, China), which were used as a training cohort to identify a signature associated with clinical outcomes. Then we conducted quantitative RT-PCR in another 103 samples of ESCC from the same cancer center as an independent cohort to verify the signature.
RESULTS
Microarray analysis showed that there were 338 lncRNAs significantly differentially expressed between ESCC and non-cancer esophagus tissues in the training cohort. From these differentially expressed lncRNAs, we found 16 lncRNAs associated with overall survival (OS) of ESCC patients using Cox regression analysis. Then a 7-lncRNA signature for predicting survival was identified from the 16 lncRNAs, which classified ESCC patients into high-risk and low-risk groups. Patients with high-risk have shorter OS (HR: 3.555, 95% CI 2.195-5.757, p < 0.001) and disease-free survival (DFS) (HR: 2.537, 95% CI 1.646-3.909, p < 0.001) when compared with patients with low-risk in the training cohort. In the independent cohort, the 7 lncRNAs were detected by qRT-PCR and used to compute risk score for the patients. The result indicates that patients with high risk also have significantly worse OS (HR = 2.662, 95% CI 1.588-4.464, p < 0.001) and DFS (HR 2.389, 95% CI 1.447-3.946, p < 0.001). The univariate and multivariate Cox regression analyses indicate that the signature is an independent factor for predicting survival of patients with ESCC. Combination of the signature and TNM staging was more powerful in predicting OS than TNM staging alone in both the training (AUC: 0.772 vs 0.681, p = 0.002) and independent cohorts (AUC: 0.772 vs 0.660, p = 0.003).
CONCLUSIONS
The 7-lncRNA signature is a potential prognostic biomarker in patients with ESCC and may help in treatment decision when combined with the TNM staging system.
背景
长链非编码 RNA（lncRNA）已被报道为许多类型癌症的预后生物标志物。我们旨在确定一种 lncRNA 特征，可以预测食管鳞状细胞癌（ESCC）患者的预后。
方法
使用定制的微阵列，我们回顾性分析了中山大学肿瘤防治中心（广州，中国）的 141 例 ESCC 样本和 81 对非癌症标本的 lncRNA 表达谱，作为训练队列，以识别与临床结果相关的特征。然后，我们在同一癌症中心的另外 103 例 ESCC 样本中进行了定量 RT-PCR，作为独立队列进行验证。
结果
微阵列分析显示，在训练队列中，ESCC 与非癌食管组织之间有 338 个 lncRNA 存在明显差异表达。通过 Cox 回归分析，我们从这些差异表达的 lncRNAs 中发现了 16 个与 ESCC 患者总生存期（OS）相关的 lncRNA。然后，从这 16 个 lncRNA 中确定了一个用于预测生存的 7-lncRNA 特征，可将 ESCC 患者分为高危和低危组。与低危组相比，高危组的 ESCC 患者 OS（HR：3.555，95%CI 2.195-5.757，p<0.001）和无病生存期（DFS）（HR：2.537，95%CI 1.646-3.909，p<0.001）更短。在独立队列中，通过 qRT-PCR 检测了 7 个 lncRNA，并用于计算患者的风险评分。结果表明，高危患者的 OS（HR=2.662，95%CI 1.588-4.464，p<0.001）和 DFS（HR 2.389，95%CI 1.447-3.946，p<0.001）也明显更差。单因素和多因素 Cox 回归分析表明，该特征是预测 ESCC 患者生存的独立因素。在训练组（AUC：0.772 与 0.681，p=0.002）和独立组（AUC：0.772 与 0.660，p=0.003）中，特征与 TNM 分期的组合在预测 OS 方面比 TNM 分期更有效。
结论
7-lncRNA 特征是 ESCC 患者潜在的预后生物标志物，当与 TNM 分期系统结合使用时，可能有助于治疗决策。
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