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长链非编码RNA图谱研究揭示了一种与食管鳞状细胞癌患者生存相关的三长链非编码RNA特征。

LncRNA profile study reveals a three-lncRNA signature associated with the survival of patients with oesophageal squamous cell carcinoma.

作者信息

Li Jiagen, Chen Zhaoli, Tian Liqing, Zhou Chengcheng, He Max Yifan, Gao Yibo, Wang Suya, Zhou Fang, Shi Susheng, Feng Xiaoli, Sun Nan, Liu Ziyuan, Skogerboe Geir, Dong Jingsi, Yao Ran, Zhao Yuda, Sun Jian, Zhang Baihua, Yu Yue, Shi Xuejiao, Luo Mei, Shao Kang, Li Ning, Qiu Bin, Tan Fengwei, Chen Runsheng, He Jie

机构信息

! Department of Thoracic Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, The People's Republic of China.

Bioinformatics Laboratory and Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing, The People's Republic of China.

出版信息

Gut. 2014 Nov;63(11):1700-10. doi: 10.1136/gutjnl-2013-305806. Epub 2014 Feb 12.

Abstract

BACKGROUND

Oesophageal cancer is one of the most deadly forms of cancer worldwide. Long non-coding RNAs (lncRNAs) are often found to have important regulatory roles.

OBJECTIVE

To assess the lncRNA expression profile of oesophageal squamous cell carcinoma (OSCC) and identify prognosis-related lncRNAs.

METHOD

LncRNA expression profiles were studied by microarray in paired tumour and normal tissues from 119 patients with OSCC and validated by qRT-PCR. The 119 patients were divided randomly into training (n=60) and test (n=59) groups. A prognostic signature was developed from the training group using a random Forest supervised classification algorithm and a nearest shrunken centroid algorithm, then validated in a test group and further, in an independent cohort (n=60). The independence of the signature in survival prediction was evaluated by multivariable Cox regression analysis.

RESULTS

LncRNAs showed significantly altered expression in OSCC tissues. From the training group, we identified a three-lncRNA signature (including the lncRNAs ENST00000435885.1, XLOC_013014 and ENST00000547963.1) which classified the patients into two groups with significantly different overall survival (median survival 19.2 months vs >60 months, p<0.0001). The signature was applied to the test group (median survival 21.5 months vs >60 months, p=0.0030) and independent cohort (median survival 25.8 months vs >48 months, p=0.0187) and showed similar prognostic values in both. Multivariable Cox regression analysis showed that the signature was an independent prognostic factor for patients with OSCC. Stratified analysis suggested that the signature was prognostic within clinical stages.

CONCLUSIONS

Our results suggest that the three-lncRNA signature is a new biomarker for the prognosis of patients with OSCC, enabling more accurate prediction of survival.

摘要

背景

食管癌是全球最致命的癌症形式之一。长链非编码RNA(lncRNA)常被发现具有重要的调控作用。

目的

评估食管鳞状细胞癌(OSCC)的lncRNA表达谱并鉴定与预后相关的lncRNA。

方法

通过微阵列研究119例OSCC患者配对的肿瘤组织和正常组织中的lncRNA表达谱,并通过qRT-PCR进行验证。119例患者被随机分为训练组(n = 60)和测试组(n = 59)。使用随机森林监督分类算法和最近收缩质心算法从训练组中开发出一种预后特征,然后在测试组中进行验证,并进一步在一个独立队列(n = 60)中进行验证。通过多变量Cox回归分析评估该特征在生存预测中的独立性。

结果

lncRNA在OSCC组织中的表达有显著改变。从训练组中,我们鉴定出一个由三个lncRNA组成的特征(包括lncRNAs ENST00000435885.1、XLOC_013014和ENST00000547963.1),该特征将患者分为两组,总体生存率有显著差异(中位生存期19.2个月对>60个月,p<0.0001)。该特征应用于测试组(中位生存期21.5个月对>60个月,p = 0.0030)和独立队列(中位生存期25.8个月对>48个月,p = 0.0187),在两者中均显示出相似的预后价值。多变量Cox回归分析表明,该特征是OSCC患者的一个独立预后因素。分层分析表明,该特征在临床分期内具有预后意义。

结论

我们的结果表明,三个lncRNA组成的特征是OSCC患者预后的一种新生物标志物,能够更准确地预测生存。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61ed/4215280/49d385c9a6d8/gutjnl-2013-305806f01.jpg

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