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

doi:10.1038/s41416-020-0742-9

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

Medical School

Liverpool University Dental Hospital
University of Liverpool

Research output: Contribution to journal › Article (journal) › peer-review

90 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 language	English
Pages (from-to)	1050-1058
Number of pages	9
Journal	British Journal of Cancer
Volume	122
Issue number	7
DOIs	https://doi.org/10.1038/s41416-020-0742-9
Publication status	Published - 1 Mar 2020

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

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10.1038/s41416-020-0742-9

Cite this

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

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.",

keywords = "Carcinoma, Non-Small-Cell Lung/genetics, Humans, Lung Neoplasms/genetics, Prognosis, RNA, Long Noncoding/genetics",

author = "Amelia Acha-Sagredo and Bubaraye Uko and Paschalia Pantazi and Bediaga, \{Naiara G\} and Chryssanthi Moschandrea and Lucille Rainbow and Marcus, \{Michael W\} and Davies, \{Michael P A\} and Field, \{John K\} and Triantafillos Liloglou",

year = "2020",

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doi = "10.1038/s41416-020-0742-9",

language = "English",

volume = "122",

pages = "1050--1058",

journal = "British Journal of Cancer",

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number = "7",

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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 -

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

Abstract

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Keywords

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