中国医学科学院肿瘤研究所赫捷教授与中科院生物物理所陈润生院士研究组合作利用lncRNA芯片系统检测了179对食管鳞状细胞癌(OSCC)和癌旁组织lncRNA表达谱。表达谱数据分为训练集、测试集和独立验证集（n=60，59和60），研究者采用Random forest法寻找生存相关的lncRNAs，并用Nearest shrunken centroid algorithm构建lncRNA表达签名。最终建立了一个包含3个lncRNA的表达签名（ENST00000435885.1, XLOC_013014 and ENST00000547963.1)，根据这3个lncRNA的表达特征可以有效区分高风险和低风险组，两组生存存在显著差异。多变量Cox回归分析显示该lncRNA表达签名是食管鳞状细胞癌的独立诊断指标，通过分层分析显示这种区分在各个临床分期的生存都存在显著差异。该研究结果已经在线发表于2014年2月12日Gut杂志上。本研究中lncRNA表达谱芯片检测工作由博奥生物集团有限公司完成。
LncRNA profile study reveals a three-lncRNA signature associated with the survival of patients with oesophageal squamous cell carcinoma
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.