Nohata Nijiro, Abba Martin C, Gutkind J Silvio
Moores Cancer Center, University of California, San Diego, La Jolla, CA, United States.
CINIBA, CONICET, School of Medical Sciences, National University of La Plata, La Plata, Argentina.
Oral Oncol. 2016 Aug;59:58-66. doi: 10.1016/j.oraloncology.2016.05.014.
The role of long non-coding RNA (lncRNA) expression in human head and neck squamous cell carcinoma (HNSCC) is still poorly understood. In this study, we aimed at establishing the onco-lncRNAome profiling of HNSCC and to identify lncRNAs correlating with prognosis and patient survival.
The Atlas of Noncoding RNAs in Cancer (TANRIC) database was employed to retrieve the lncRNA expression information generated from The Cancer Genome Atlas (TCGA) HNSCC RNA-sequencing data. RNA-sequencing data from HNSCC cell lines were also considered for this study. Bioinformatics approaches, such as differential gene expression analysis, survival analysis, principal component analysis, and Co-LncRNA enrichment analysis were performed.
Using TCGA HNSCC RNA-sequencing data from 426 HNSCC and 42 adjacent normal tissues, we found 728 lncRNA transcripts significantly and differentially expressed in HNSCC. Among the 728 lncRNAs, 55 lncRNAs were significantly associated with poor prognosis, such as overall survival and/or disease-free survival. Next, we found 140 lncRNA transcripts significantly and differentially expressed between Human Papilloma Virus (HPV) positive tumors and HPV negative tumors. Thirty lncRNA transcripts were differentially expressed between TP53 mutated and TP53 wild type tumors. Co-LncRNA analysis suggested that protein-coding genes that are co-expressed with these deregulated lncRNAs might be involved in cancer associated molecular events. With consideration of differential expression of lncRNAs in a HNSCC cell lines panel (n=22), we found several lncRNAs that may represent potential targets for diagnosis, therapy and prevention of HNSCC.
LncRNAs profiling could provide novel insights into the potential mechanisms of HNSCC oncogenesis.
长链非编码RNA（lncRNA）表达在人类头颈部鳞状细胞癌（HNSCC）中的作用仍知之甚少。在本研究中，我们旨在建立HNSCC的肿瘤lncRNA图谱，并鉴定与预后和患者生存相关的lncRNA。
利用癌症非编码RNA图谱（TANRIC）数据库检索来自癌症基因组图谱（TCGA）HNSCC RNA测序数据的lncRNA表达信息。本研究还考虑了HNSCC细胞系的RNA测序数据。进行了生物信息学分析，如差异基因表达分析、生存分析、主成分分析和共lncRNA富集分析。
使用来自426例HNSCC和42例相邻正常组织的TCGA HNSCC RNA测序数据，我们发现728个lncRNA转录本在HNSCC中显著差异表达。在这728个lncRNA中，55个lncRNA与不良预后显著相关，如总生存和/或无病生存。接下来，我们发现140个lncRNA转录本在人乳头瘤病毒（HPV）阳性肿瘤和HPV阴性肿瘤之间显著差异表达。30个lncRNA转录本在TP53突变型和TP53野生型肿瘤之间差异表达。共lncRNA分析表明，与这些失调的lncRNA共表达的蛋白质编码基因可能参与癌症相关分子事件。考虑到lncRNA在一组HNSCC细胞系（n = 22）中的差异表达，我们发现了几个可能代表HNSCC诊断、治疗和预防潜在靶点的lncRNA。
lncRNA图谱可为HNSCC肿瘤发生的潜在机制提供新的见解。
