Abstract
BackgroundMany long non-coding RNAs(lncRNAs) have been found to be a good marker for several tumors. Using lncRNA-mining approach, we aimed to identify lncRNA expression signature that can predict breast cancer patient survival.MethodsWe performed LncRNA expression profiling in 887 breast cancer patients from Gene Expression Omnibus (GEO) datasets. The association between lncRNA signature and clinical survival was analyzed using the training set(n = 327, from GSE 20685). The validation for the association was performed in another three independent testing sets(252 from GSE21653, 204 from GSE12276, and 104 from GSE42568).ResultsA set of four lncRNA genes (U79277, AK024118, BC040204, AK000974) have been identified by the random survival forest algorithm. Using a risk score based on the expression signature of these lncRNAs, we separated the patients into low-risk and high-risk groups with significantly different survival times in the training set. This signature was validated in the other three cohorts. Further study revealed that the four-lncRNA expression signature was independent of age and subtype. Gene Set Enrichment Analysis (GSEA) suggested that gene sets were involved in several cancer metastasis related pathways.ConclusionsThese findings indicate that lncRNAs may be implicated in breast cancer pathogenesis. The four-lncRNA signature may have clinical implications in the selection of high-risk patients for adjuvant therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-014-0084-7) contains supplementary material, which is available to authorized users.
Highlights
Many long non-coding RNAs(lncRNAs) have been found to be a good marker for several tumors
We identified a four-lncRNA signature associated with survival, and established a risk score formula using the expressions of these four lncRNAs
By subjecting the lncRNA expression data derived from the training set to univariable Cox proportional hazards regression analysis using the BRB-Array Tools, we identified a set of 30 lncRNAs that were strongly correlated with patients’ overall survival (P ≤ 0.001)
Summary
Many long non-coding RNAs(lncRNAs) have been found to be a good marker for several tumors. More than 50% of transcripts have no protein coding potential through the analysis of mammalian transcriptomes, a subset of these noncoding transcripts are termed long non-coding RNAs (lncRNAs) that range from 200 nucleotides to multiple kilobases in length [1]. One of the examples is a 21-gene classifer (Oncotype DX) ,which classifies breast tumors into low,intermediate- and high-risk groups as to the advisability of adjuvant chemotherapy for patients in high-risk group [12,13] The utility of such gene signature might have clinical potential to predict patient outcome and aid in treatment choice [14]
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