Long non-coding RNA dysregulation is a frequent event in non-small cell lung carcinoma pathogenesis

Amelia Acha-Sagredo, Bubaraye Uko, Paschalia Pantazi, Naiara G Bediaga, Chryssanthi Moschandrea, Lucille Rainbow, Michael W Marcus, Michael P A Davies, John K Field, Triantafillos Liloglou

Research output: Contribution to journalArticle (journal)peer-review

71 Citations (Scopus)

Abstract

BACKGROUND: Long non-coding RNAs compose an important level of epigenetic regulation in normal physiology and disease. Despite the plethora of publications of lncRNAs in human cancer, the landscape is still unclear.

METHODS: Microarray analysis in 44 NSCLC paired specimens was followed by qPCR-based validation in 29 (technical) and 38 (independent) tissue pairs. Cross-validation of the selected targets was achieved in 850 NSCLC tumours from TCGA datasets.

RESULTS: Twelve targets were successfully validated by qPCR (upregulated: FEZF1-AS1, LINC01214, LINC00673, PCAT6, NUTM2A-AS1, LINC01929; downregulated: PCAT19, FENDRR, SVIL-AS1, LANCL1-AS1, ADAMTS9-AS2 and LINC00968). All of them were successfully cross validated in the TCGA datasets. Abnormal DNA methylation was observed in the promoters of FENDRR, FEZF1-AS1 and SVIL-AS1. FEZF1-AS1 and LINC01929 were associated with survival in the TCGA set.

CONCLUSIONS: Our study provides through multiple levels of internal and external validation, a comprehensive list of dysregulated lncRNAs in NSCLC. We therefore envisage this dataset to serve as an important source for the lung cancer research community assisting future investigations on the involvement of lncRNAs in the pathogenesis of the disease and providing novel biomarkers for diagnosis, prognosis and therapeutic stratification.

Original languageEnglish
Pages (from-to)1050-1058
Number of pages9
JournalBritish Journal of Cancer
Volume122
Issue number7
DOIs
Publication statusPublished - 1 Mar 2020

Keywords

  • Carcinoma, Non-Small-Cell Lung/genetics
  • Humans
  • Lung Neoplasms/genetics
  • Prognosis
  • RNA, Long Noncoding/genetics

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