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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.


Kaplan-Meier plots for Overall Survival.Probability of OS is plotted over time and the Kaplan-Meier plots indicate that in both Case-control (a) and Case-only (b) approaches of discovery cohort, patients belonging to high-risk group are associated with poorer OS. A similar trend in survival pattern was observed in the external dataset/TCGA (c). (d) Probability of RFS is plotted over time and the Kaplan-Meier plots indicate that in the CO approach, patients belonging to high-risk group are associated with poorer RFS.
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f2: Kaplan-Meier plots for Overall Survival.Probability of OS is plotted over time and the Kaplan-Meier plots indicate that in both Case-control (a) and Case-only (b) approaches of discovery cohort, patients belonging to high-risk group are associated with poorer OS. A similar trend in survival pattern was observed in the external dataset/TCGA (c). (d) Probability of RFS is plotted over time and the Kaplan-Meier plots indicate that in the CO approach, patients belonging to high-risk group are associated with poorer RFS.

Mentions: In the CC approach, survival analysis was restricted to 76 DE tRNAs that were subjected to univariate Cox proportional hazards regression model followed by permutation test. We found three tRNAs (chr6.tRNA5-SerAGA, chr6.tRNA50-SerAGA and chr6.tRNA51-SerTGA) associated with OS that had a permutation p-value ≤ 0.1 (Table 1). These three tRNAs were used to construct a risk score for all cases, and then the cases were dichotomized into two groups based on the ROC estimated cut-off point (3.06). Cases with a risk score ≤3.06 and >3.06 were classified as low-risk and high-risk groups, respectively. Further, the risk score was adjusted for tumor stage and age at diagnosis. High-risk group patients were found to have shorter OS (hazard ratio, HR = 2.68, p = 0.02, CI = 1.19–5.99; Table 2, Fig. 2a). Interestingly, none of the DE tRNAs were found to be associated with RFS.


Genome-wide profiling of transfer RNAs and their role as novel prognostic markers for breast cancer
Kaplan-Meier plots for Overall Survival.Probability of OS is plotted over time and the Kaplan-Meier plots indicate that in both Case-control (a) and Case-only (b) approaches of discovery cohort, patients belonging to high-risk group are associated with poorer OS. A similar trend in survival pattern was observed in the external dataset/TCGA (c). (d) Probability of RFS is plotted over time and the Kaplan-Meier plots indicate that in the CO approach, patients belonging to high-risk group are associated with poorer RFS.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Kaplan-Meier plots for Overall Survival.Probability of OS is plotted over time and the Kaplan-Meier plots indicate that in both Case-control (a) and Case-only (b) approaches of discovery cohort, patients belonging to high-risk group are associated with poorer OS. A similar trend in survival pattern was observed in the external dataset/TCGA (c). (d) Probability of RFS is plotted over time and the Kaplan-Meier plots indicate that in the CO approach, patients belonging to high-risk group are associated with poorer RFS.
Mentions: In the CC approach, survival analysis was restricted to 76 DE tRNAs that were subjected to univariate Cox proportional hazards regression model followed by permutation test. We found three tRNAs (chr6.tRNA5-SerAGA, chr6.tRNA50-SerAGA and chr6.tRNA51-SerTGA) associated with OS that had a permutation p-value ≤ 0.1 (Table 1). These three tRNAs were used to construct a risk score for all cases, and then the cases were dichotomized into two groups based on the ROC estimated cut-off point (3.06). Cases with a risk score ≤3.06 and >3.06 were classified as low-risk and high-risk groups, respectively. Further, the risk score was adjusted for tumor stage and age at diagnosis. High-risk group patients were found to have shorter OS (hazard ratio, HR = 2.68, p = 0.02, CI = 1.19–5.99; Table 2, Fig. 2a). Interestingly, none of the DE tRNAs were found to be associated with RFS.

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.