LncRNA profile study reveals a three-lncRNA signature associated with the survival of patients with oesophageal squamous cell carcinoma.
LncRNA profile study reveals a three-lncRNA signature associated with the survival of patients with oesophageal squamous cell carcinoma.
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作者：
Li J;Chen Z;Tian L;Zhou C;He MY;Gao Y;Wang S;Zhou F;Shi S;Feng X;Sun N;Liu Z;Skogerboe G;Dong J;Yao R;Zhao Y;Sun J;Zhang B;Yu Y;Shi X;Luo M;Shao K;Li N;Qiu B;Tan F;Chen R;He J
食管癌是世界上最致命的癌症之一。长链非编码rna （lncrna）经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。采用微阵列技术研究了119例OSCC患者配对肿瘤和正常组织中LncRNA的表达谱，并采用qRT-PCR技术进行了验证。119例患者随机分为训练组（n=60）和试验组（n=59）。使用随机Forest监督分类算法和最近萎缩质心算法从训练组中开发预后签名，然后在试验组和独立队列中进一步验证（n=60）。通过多变量Cox回归分析评估特征在生存预测中的独立性。LncRNAs在OSCC组织中的表达明显改变。从训练组中，我们发现了三个lncrna特征（包括ENST00000435885.1、XLOC_013014和ENST00000547963.1），将患者分为两组，总生存期显著不同（中位生存期19.2个月vs中位生存期60个月，p<0.0001）。该特征应用于试验组（中位生存期21.5个月vs >60个月，p=0.0030）和独立队列（中位生存期25.8个月vs >48个月，p=0.0187），两者的预后价值相似。多变量Cox回归分析显示，该特征是影响OSCC患者预后的独立因素。分层分析表明，该特征在临床分期内具有预后性。我们的研究结果表明，三lncrna标记是OSCC患者预后的一种新的生物标志物，可以更准确地预测生存。
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. To assess the lncRNA expression profile of oesophageal squamous cell carcinoma (OSCC) and identify prognosis-related lncRNAs. 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. 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. 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.
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