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Comprehensive landscape of subtype-specific coding and non-coding RNA transcripts in breast cancer
- Title
- Comprehensive landscape of subtype-specific coding and non-coding RNA transcripts in breast cancer
- Authors
- Vu, Trung Nghia; Pramana, Setia; Calza, Stefano; Suo, Chen; Lee, Donghwan; Pawitan, Yudi
- Ewha Authors
- 이동환
- SCOPUS Author ID
- 이동환
- Issue Date
- 2016
- Journal Title
- ONCOTARGET
- ISSN
- 1949-2553
- Citation
- ONCOTARGET vol. 7, no. 42, pp. 68851 - 68863
- Keywords
- breast cancer; RNA sequencing; subtype-specific isoforms; subtype co-expression; non-coding RNAs
- Publisher
- IMPACT JOURNALS LLC
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Molecular classification of breast cancer into clinically relevant subtypes helps improve prognosis and adjuvant-treatment decisions. The aim of this study is to provide a better characterization of the molecular subtypes by providing a comprehensive landscape of subtype-specific isoforms including coding, long non-coding RNA and microRNA transcripts. Isoform-level expression of all coding and non-coding RNAs is estimated from RNA-sequence data of 1168 breast samples obtained from The Cancer Genome Atlas (TCGA) project. We then search the whole transcriptome systematically for subtype-specific isoforms using a novel algorithm based on a robust quasi-Poisson model. We discover 5451 isoforms specific to single subtypes. A total of 27% of the subtype-specific isoforms have better accuracy in classifying the intrinsic subtypes than that of their corresponding genes. We find three subtype-specific miRNA and 707 subtype-specific long non-coding RNAs. The isoforms from long non-coding RNAs also show high performance for separation between Luminal A and Luminal B subtypes with an AUC of 0.97 in the discovery set and 0.90 in the validation set. In addition, we discover 1500 isoforms preferentially co-expressed in two subtypes, including 369 isoforms co-expressed in both Normal-like and Basal subtypes, which are commonly considered to have distinct ER-receptor status. Finally, analyses at protein level reveal four subtype-specific proteins and two subtype co-expression proteins that successfully validate results from the isoform level.
- DOI
- 10.18632/oncotarget.11998
- Appears in Collections:
- 자연과학대학 > 통계학전공 > Journal papers
- Files in This Item:
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