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.
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.
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.
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.
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We would like to thank Dr. Gordon K. Smyth and Dr Ramyar Molania from the Walter & Eliza Hall Institute of Medical Research, Melbourne, Australia for their invaluable assistance in the bioinformatics analysis. We would also want to acknowledge the voluntary contribution of patients with their specimens and information as well as the nursing staff that recruited them in the study.
Ethics approval and consent to participate
Ethical approval was obtained from the Liverpool Central Research Ethics Committee (ref 97/141). All patients were recruited following voluntary informed consent, and the study was performed in accordance with the Declaration of Helsinki.
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Microarray data have been deposited in the Gene Expression Omnibus (GEO) database (GSE130740).
The authors declare no competing interests.
This research was supported by the Roy Castle Lung Cancer Foundation, UK (Grant no 2014/05/Liloglou) and a Roy Castle Lung Cancer Senior Fellowship (MPAD).
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Acha-Sagredo, A., Uko, B., Pantazi, P. et al. Long non-coding RNA dysregulation is a frequent event in non-small cell lung carcinoma pathogenesis. Br J Cancer 122, 1050–1058 (2020). https://doi.org/10.1038/s41416-020-0742-9
International Journal of Molecular Sciences (2020)