Dang Ha X, White Nicole M, Rozycki Emily B, Felsheim Brooke M, Watson Mark A, Govindan Ramaswamy, Luo Jingqin, Maher Christopher A
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA.
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
Heliyon. 2020 Mar 5;6(3):e03521. doi: 10.1016/j.heliyon.2020.e03521. eCollection 2020 Mar.
More than half of non-small cell lung cancer (NSCLC) patients present with metastatic disease at initial diagnosis with an estimated five-year survival rate of ~5%. Despite advances in understanding primary lung cancer oncogenesis metastatic disease remains poorly characterized. Recent studies demonstrate important roles of long non-coding RNAs (lncRNAs) in tumor physiology and as prognostic markers. Therefore, we present the first transcriptome analysis to identify lncRNAs altered in metastatic lung adenocarcinoma leading to the discovery and characterization of the lncRNA as a prognostic biomarker.
RNA-Seq, microarray, nanoString expression, and clinical data from 1,116 LUAD patients across six independent cohorts and 83 LUAD cell lines were used to discover and evaluate the survival association of metastasis associated lncRNAs. Coexpression and gene set enrichment analyses were used to establish gene regulatory networks and implicate metastasis associated lncRNAs in specific biological processes.
Our integrative analysis discovered as the most down-regulated lncRNA in metastasis. Further low expression promoted aggressive phenotypes and regulated genes associated with metastasis (such as metastasis repressor ). Low expression corresponded to poor overall patient survival across five independent lung adenocarcinoma cohorts ( = 881) including our own nanoString validation cohort.
We discovered that was down-regulated in lung cancer progression to promote invasive phenotypes, and lower expression was significantly associated with poor patient outcome and aggressive lung adenocarcinoma.
超过半数的非小细胞肺癌（NSCLC）患者在初次诊断时就已出现转移性疾病，其估计五年生存率约为5%。尽管在理解原发性肺癌的肿瘤发生方面取得了进展，但转移性疾病的特征仍知之甚少。最近的研究表明长链非编码RNA（lncRNA）在肿瘤生理学中具有重要作用，并可作为预后标志物。因此，我们进行了首次转录组分析，以鉴定转移性肺腺癌中发生改变的lncRNA，从而发现并表征lncRNA作为一种预后生物标志物。
来自六个独立队列的1116例肺腺癌（LUAD）患者和83个LUAD细胞系的RNA测序、微阵列、纳米串表达及临床数据，用于发现和评估与转移相关lncRNA的生存关联。共表达和基因集富集分析用于建立基因调控网络，并将与转移相关的lncRNA牵涉到特定的生物学过程中。
我们的综合分析发现[具体lncRNA名称未给出]是转移过程中下调最明显的lncRNA。进一步研究发现，其低表达促进了侵袭性表型，并调控了与转移相关的基因（如转移抑制因子）。在包括我们自己的纳米串验证队列在内的五个独立肺腺癌队列（n = 881）中，[具体lncRNA名称未给出]的低表达与患者总体生存情况较差相对应。
我们发现[具体lncRNA名称未给出]在肺癌进展过程中下调，以促进侵袭性表型，其低表达与患者预后不良及侵袭性肺腺癌显著相关。
