Genome-wide profiling of transfer RNAs and their role as novel prognostic markers for breast cancer.
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.
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, T6G 2R3, Canada.
Preethi
P
Krishnan
Department of Oncology, University of Alberta, Edmonton, Alberta, T6G 1Z2, Canada.|Cross Cancer Institute, Alberta Health Services, Edmonton, Alberta, T6G 1Z2, Canada.
Sunita
S
Ghosh
Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, T1K 3M4, Canada.
Bo
B
Wang
Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, T1K 3M4, Canada.
Mieke
M
Heyns
Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, T1K 3M4, Canada.
Dongping
D
Li
Department of Oncology, University of Alberta, Edmonton, Alberta, T6G 1Z2, Canada.|Cross Cancer Institute, Alberta Health Services, Edmonton, Alberta, T6G 1Z2, Canada.
John R
JR
Mackey
Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, T1K 3M4, Canada.
Olga
O
Kovalchuk
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, T6G 2R3, Canada.|Cross Cancer Institute, Alberta Health Services, Edmonton, Alberta, T6G 1Z2, Canada.
Sambasivarao
S
Damaraju
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011379:Prognosis; D012343:RNA, Transfer / Q000235:genetics*; D015854:Up-Regulation; D055815:Young Adult
D014408:Biomarkers, Tumor; D012343:RNA, Transfer