TY - JOUR
T1 - Long non-coding RNA dysregulation is a frequent event in non-small cell lung carcinoma pathogenesis
AU - Acha-Sagredo, Amelia
AU - Uko, Bubaraye
AU - Pantazi, Paschalia
AU - Bediaga, Naiara G
AU - Moschandrea, Chryssanthi
AU - Rainbow, Lucille
AU - Marcus, Michael W
AU - Davies, Michael P A
AU - Field, John K
AU - Liloglou, Triantafillos
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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.
AB - 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.
KW - Carcinoma, Non-Small-Cell Lung/genetics
KW - Humans
KW - Lung Neoplasms/genetics
KW - Prognosis
KW - RNA, Long Noncoding/genetics
U2 - 10.1038/s41416-020-0742-9
DO - 10.1038/s41416-020-0742-9
M3 - Article (journal)
C2 - 32020063
SN - 0007-0920
VL - 122
SP - 1050
EP - 1058
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 7
ER -