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Genome-wide profiling of transfer RNAs and their role as novel prognostic markers for breast cancer

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

qRT-PCR validation of up-regulated tRNAs.qRT-PCR results of two representative tRNAs confirm their up-regulation in tumors (using GAPDH as the internal normalizer), as indicated by initial NGS experiments. *p < 0.05.
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f3: qRT-PCR validation of up-regulated tRNAs.qRT-PCR results of two representative tRNAs confirm their up-regulation in tumors (using GAPDH as the internal normalizer), as indicated by initial NGS experiments. *p < 0.05.

Mentions: Two representative tRNAs, chr6.tRNA50-SerAGA and chr6.tRNA51-SerTGA, exhibiting a fold change of 2.56 and 2.61, respectively in next generation sequencing (NGS) platform, were validated using qRT-PCR. Both tRNAs were found to be up-regulated in tumors relative to normal tissues in qRT-PCR experiments (Fig. 3), confirming the findings from NGS.


Genome-wide profiling of transfer RNAs and their role as novel prognostic markers for breast cancer
qRT-PCR validation of up-regulated tRNAs.qRT-PCR results of two representative tRNAs confirm their up-regulation in tumors (using GAPDH as the internal normalizer), as indicated by initial NGS experiments. *p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5015097&req=5

f3: qRT-PCR validation of up-regulated tRNAs.qRT-PCR results of two representative tRNAs confirm their up-regulation in tumors (using GAPDH as the internal normalizer), as indicated by initial NGS experiments. *p < 0.05.
Mentions: Two representative tRNAs, chr6.tRNA50-SerAGA and chr6.tRNA51-SerTGA, exhibiting a fold change of 2.56 and 2.61, respectively in next generation sequencing (NGS) platform, were validated using qRT-PCR. Both tRNAs were found to be up-regulated in tumors relative to normal tissues in qRT-PCR experiments (Fig. 3), confirming the findings from NGS.

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus