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

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 × 10−6, 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0666-z) contains supplementary material, which is available to authorized users.

Systematic identification of lincRNA‐based prognostic biomarkers by integrating lincRNA expression and copy number variation in lung adenocarcinoma

“…Previous studies analyzed the gene expression profiles of LUAD patient samples to identify prognostic biomarkers and classified the lung cancer subtypes based on gene expression . RNA‐Seq data show that some long noncoding RNAs (lncRNAs) such as C1orf132 and TMPO‐AS1 are associated with increased risk of LUAD and show potential as prognostic biomarkers . Studies based on single nucleotide polymorphism (SNP) arrays and targeted sequencing or whole‐genome/exome sequencing of protein‐coding genes (PCGs) have identified somatic mutations, focal amplifications or copy number alterations in many oncogenes and tumor suppressor genes such as RIT1 and MGA in LUAD patients .…”

“…7,8 RNA-Seq data show that some long noncoding RNAs (lncRNAs) such as C1orf132 and TMPO-AS1 are associated with increased risk of LUAD and show potential as prognostic biomarkers. [9][10][11][12] Studies based on single nucleotide polymorphism (SNP) arrays and targeted sequencing or wholegenome/exome sequencing of protein-coding genes (PCGs) have identified somatic mutations, focal amplifications or copy number alterations in many oncogenes and tumor suppressor genes such as RIT1 and MGA in LUAD patients. 13,14 In human cancers, copy number alterations (CNAs) are the most common type of genetic alterations; they influence activation of oncogenes and repression of tumor suppressor genes.…”

Unique metastasis‐associated lncRNA signature optimizes prediction of tumor relapse in lung adenocarcinoma

“…Increasing evidence shows that lncRNAs play a critical role in cancer biology. Dysregulation of lncRNAs often serves as an independent predictor for poor prognosis of cancer patients . Our group has previously reported that circulating lncRNAs act as potential novel biomarkers for diagnosis and prognosis of non‐small cell lung cancer .…”

“…Dysregulation of lncRNAs often serves as an independent predictor for poor prognosis of cancer patients. [5][6][7][8][9] Our group has previously reported that circulating lncRNAs act as potential novel biomarkers for diagnosis and prognosis of non-small cell lung cancer. 10 Several recent studies have focused on the involvement of lncRNAs in tumor metastasis because these lncRNAs have shown great promise in the discovery of new biomarkers for predicting prognosis in individual patients.…”

<p>Long Non-Coding RNA TMPO-AS1 Promotes Cervical Cancer Cell Proliferation, Migration, and Invasion by Regulating miR-143-3p/ZEB1 Axis</p>

“…TMPO-AS1 could also affect the prognosis of patients with lung adenocarcinoma through regulating cell cycle and cell adhesion. 6 With regard to cervical cancer, Liu et al 7 showed that TMPO-AS1 was highly expressed in the cervical cancer tissues when compared with the adjacent tissues according to chip analysis. However, the expression of TMPO-AS1 in cervical cancer cells and its exact role in cervical cancer remain unclear.…”