Yao Yao, Chen Xinyuan, Lu Shuai, Zhou Chao, Xu Guolong, Yan Zhongyi, Yang Jianrong, Yu Tonghua, Chen Wei, Qian Yichun, Ding Shounian, Tang Junwei, Chen Yun, Zhang Yuan
Department of Head and Neck Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China.
Department of Immunology, Nanjing Medical University, Nanjing, China.
Cell Physiol Biochem. 2018;50(4):1429-1440. doi: 10.1159/000494605. Epub 2018 Oct 24.
BACKGROUND/AIMS: The anatomical complexity of the head and neck region and the lack of sufficiently specific and sensitive biomarkers often lead to the diagnosis of head and neck squamous cell carcinoma (HNSCC) at advanced stages. To identify novel biomarkers for early diagnosis of primary HNSCC through a minimally invasive method, we investigated circulating long noncoding RNA (lncRNA) levels in plasma of HNSCC patients.
The global lncRNA expression profiles of HNSCC patients were measured using microarray and next-generation RNA-sequencing (RNA-seq) data from both circulating and tissue samples. The diagnosis prediction model based on the lncRNA signatures and clinical features was evaluated by multi-stage validation and risk score analysis.
The data showed that 432 lncRNA transcripts were differentially expressed by fold changes of > 4 in circulating samples and 333 in tissues samples, respectively. Only 12 lncRNAs consistently emerged in these two kinds of samples. After the risk score analysis including a multistage validation, we identified three lncRNAs, namely, HOXA11-AS, LINC00964 and MALAT1, which were up-regulated in the plasma of HNSCC patients compared with those in healthy controls with merged areas under the curve (AUCs) in training and validation sets of 0.925 and 0.839, respectively.
HOXA11-AS, LINC00964 and MALAT1 might be potential circulating biomarkers for the early detection of HNSCC in the future.
背景/目的:头颈部区域的解剖结构复杂,且缺乏足够特异和敏感的生物标志物,这常常导致头颈部鳞状细胞癌(HNSCC)在晚期才得以诊断。为了通过微创方法鉴定用于原发性HNSCC早期诊断的新型生物标志物,我们研究了HNSCC患者血浆中循环长链非编码RNA(lncRNA)的水平。
使用来自循环样本和组织样本的微阵列以及下一代RNA测序(RNA-seq)数据测量HNSCC患者的整体lncRNA表达谱。基于lncRNA特征和临床特征的诊断预测模型通过多阶段验证和风险评分分析进行评估。
数据显示,循环样本中432个lncRNA转录本的表达变化倍数>4,组织样本中为333个,差异表达。在这两种样本中仅一致出现了12种lncRNA。经过包括多阶段验证的风险评分分析后,我们鉴定出三种lncRNA,即HOXA11-AS、LINC00964和MALAT1,与健康对照相比,它们在HNSCC患者血浆中上调,训练集和验证集的合并曲线下面积(AUC)分别为0.925和0.839。
HOXA11-AS、LINC00964和MALAT1未来可能是用于HNSCC早期检测的潜在循环生物标志物。