Abstract
Breast cancer is a complex disease, characterized by gene deregulation. There is less systematic investigation of the capacity of long intergenic non-coding RNAs (lincRNAs) as biomarkers associated with breast cancer pathogenesis or several clinicopathological variables including receptor status and patient survival. We designed a two-stage study, including 1,000 breast tumor RNA-seq data from The Cancer Genome Atlas (TCGA) as the discovery stage, and RNA-seq data of matched tumor and adjacent normal tissue from 50 breast cancer patients as well as 23 normal breast tissue from healthy women as the replication stage. We identified 83 lincRNAs showing the significant expression changes in breast tumors with a false discovery rate (FDR) < 1% in the discovery dataset. Thirty-seven out of the 83 were validated in the replication dataset. Integrative genomic analyses suggested that the aberrant expression of these 37 lincRNAs was probably related with the expression alteration of several transcription factors (TFs). We observed a differential co-expression pattern between lincRNAs and their neighboring genes. We found that the expression levels of one lincRNA (RP5-1198O20 with Ensembl ID ENSG00000230615) were associated with breast cancer survival with P < 0.05. Our study identifies a set of aberrantly expressed lincRNAs in breast cancer.
Highlights
The advances in high-throughput sequencing technologies provide a systematic landscape in the complexity of transcriptome, especially the discovery of a wealth of long non-coding transcripts[1,2]
The Cancer Genome Atlas (TCGA) has revealed that the aberrant expression of hundreds of protein-coding genes and tens of microRNAs are associated with breast cancer development, progression, metastasis[13,14,15,16] and subtypes[17,18]
Our work substantially extends the biological understanding of the lincRNA repertoire in the pathogenesis of breast cancer
Summary
The advances in high-throughput sequencing technologies provide a systematic landscape in the complexity of transcriptome, especially the discovery of a wealth of long non-coding transcripts[1,2]. This phenomenon is referred to as pervasive transcription[3], albeit some transcripts are probably the byproduct of the transcription noise[4]. The Cancer Genome Atlas (TCGA) has revealed that the aberrant expression of hundreds of protein-coding genes and tens of microRNAs are associated with breast cancer development, progression, metastasis[13,14,15,16] and subtypes[17,18]. No of samples Age (yr ± s.d.) Ethnicity White Asian Black Unknown ER status ER+ER− Unknown Stage 0-I II III IV Unknown
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