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Published in: Molecular Cancer 1/2017

Open Access 01-12-2017 | Research

Differential expression analysis at the individual level reveals a lncRNA prognostic signature for lung adenocarcinoma

Authors: Fuduan Peng, Ruiping Wang, Yuanyuan Zhang, Zhangxiang Zhao, Wenbin Zhou, Zhiqiang Chang, Haihai Liang, Wenyuan Zhao, Lishuang Qi, Zheng Guo, Yunyan Gu

Published in: Molecular Cancer | Issue 1/2017

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Abstract

Background

Deregulations 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.

Methods

We 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.

Results

In 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 × 10−6, log-rank test), which was confirmed in two independent datasets of GSE50081 (P = 1.82 × 10−2, log-rank test) and GSE31210 (P = 7.43 × 10−4, 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.

Conclusions

LncRIndiv can successfully detect DE lncRNAs in individuals and be applied to identify prognostic signature for LUAD patients.
Appendix
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Metadata
Title
Differential expression analysis at the individual level reveals a lncRNA prognostic signature for lung adenocarcinoma
Authors
Fuduan Peng
Ruiping Wang
Yuanyuan Zhang
Zhangxiang Zhao
Wenbin Zhou
Zhiqiang Chang
Haihai Liang
Wenyuan Zhao
Lishuang Qi
Zheng Guo
Yunyan Gu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2017
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-017-0666-z

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