Genome-wide profiling of transfer RNAs and their role as novel prognostic markers for breast cancer
Date
2016
Authors
Krishnan, Preethi
Ghosh, Sunita
Wang, Bo
Heyns, Mieke
Li, Dongping
Mackey, John R.
Kovalchuk, Olga
Damaraju, Sambasivarao
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Publishing Group
Abstract
Transfer RNAs (tRNAs, key molecules in protein synthesis) have not been investigated as potential
prognostic markers in breast cancer (BC), despite early findings of their dysregulation and diagnostic
potential. We aim to comprehensively profile tRNAs from breast tissues and to evaluate their role as
prognostic markers (Overall Survival, OS and Recurrence Free Survival, RFS). tRNAs were profiled
from 11 normal breast and 104 breast tumor tissues using next generation sequencing. We adopted a
Case-control (CC) and Case-Only (CO) association study designs. Risk scores constructed from tRNAs
were subjected to univariate and multivariate Cox-proportional hazards regression to investigate
their prognostic value. Of the 571 tRNAs profiled, 76 were differentially expressed (DE) and three
were significant for OS in the CC approach. We identified an additional 11 tRNAs associated with OS
and 14 tRNAs as significant for RFS in the CO approach, indicating that CC alone may not capture all
discriminatory tRNAs in prognoses. In both the approaches, the risk scores were significant in the
multivariate analysis as independent prognostic factors, and patients belonging to high-risk group
were associated with poor prognosis. Our results confirmed global up-regulation of tRNAs in BC and
identified tRNAs as potential novel prognostic markers for BC.
Description
Sherpa Romeo green journal: open access
Keywords
Transfer RNAs , Prognostic marker , Overall survival , Recurrence free survival , Breast cancer , Next generation sequencing
Citation
Krishnan, P., Ghosh, S., Wang, B., Heyns, M., Li, D., Mackey, J.R. ...Damaraju, S. (2016). Genome-wide profling of transfer RNAs and their role as novel prognostic markers for breast cancer. Scientific Report, 6, 32843. doi:10.1038/srep32483(2016)