Differential expression analysis at the individual level reveals a lncRNA prognostic signature for lung adenocarcinomaReport as inadecuate




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Molecular Cancer

, 16:98

First Online: 06 June 2017Received: 25 August 2016Accepted: 22 May 2017DOI: 10.1186-s12943-017-0666-z

Cite this article as: Peng, F., Wang, R., Zhang, Y. et al. Mol Cancer 2017 16: 98. doi:10.1186-s12943-017-0666-z

Abstract

BackgroundDeregulations of long non-coding RNAs lncRNAs have been implicated in cancer initiation and progression. Current methods can only capture differential expression of lncRNAs at the population level and ignore the heterogeneous expression of lncRNAs in individual patients.

MethodsWe propose a method LncRIndiv to identify differentially expressed DE lncRNAs in individual cancer patients by exploiting the disrupted ordering of expression levels of lncRNAs in each disease sample in comparison with stable normal ordering. LncRIndiv was applied to lncRNA expression profiles of lung adenocarcinoma LUAD. Based on the expression profile of LUAD individual-level DE lncRNAs, we used a forward selection procedure to identify prognostic signature for stage I-II LUAD patients without adjuvant therapy.

ResultsIn both simulated data and real pair-wise cancer and normal sample data, LncRIndiv method showed good performance. Based on the individual-level DE lncRNAs, we developed a robust prognostic signature consisting of two lncRNA C1orf132 and TMPO-AS1 for stage I-II LUAD patients without adjuvant therapy P = 3.06 × 10, log-rank test, which was confirmed in two independent datasets of GSE50081 P = 1.82 × 10, log-rank test and GSE31210 P = 7.43 × 10, log-rank test after adjusting other clinical factors such as smoking status and stages. Pathway analysis showed that TMPO-AS1 and C1orf132 could affect the prognosis of LUAD patients through regulating cell cycle and cell adhesion.

ConclusionsLncRIndiv can successfully detect DE lncRNAs in individuals and be applied to identify prognostic signature for LUAD patients.

KeywordslncRNAs differentially expressed lncRNA Lung adenocarcinoma Prognostic signature Individual level AbbreviationsC-indexHarrell’s concordance index

CVCoefficient of variation

DEDifferentially expressed

DEGsDifferentially expressed genes

FDRFalse Discovery Rate

FPFalse positive

GOGene Ontology

KEGGKyoto Encyclopedia of Genes and Genomes

lncRNAsLong non-coding RNAs

LUADLung adenocarcinoma

TANRICThe Atlas of Noncoding RNAs in Cancer

TCGAThe Cancer Genome Atlas

TPTrue positive

Electronic supplementary materialThe online version of this article doi:10.1186-s12943-017-0666-z contains supplementary material, which is available to authorized users.

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Author: Fuduan Peng - Ruiping Wang - Yuanyuan Zhang - Zhangxiang Zhao - Wenbin Zhou - Zhiqiang Chang - Haihai Liang - Wenyuan Zhao

Source: https://link.springer.com/







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