Plasma tsRNA Signatures Serve as a Novel Biomarker for Bladder Cancer

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Bladder cancer (BLCA) diagnosis relies on invasive methods, highlighting the need for non-invasive early detection biomarkers.
• Current non-invasive diagnostic tools for BLCA lack sufficient sensitivity and specificity.
• tRNA-derived small RNAs (tsRNAs) are emerging as functional non-coding RNAs with potential diagnostic applications in various cancers.

Purpose of the Study:

• To identify novel non-coding RNA biomarkers for early bladder cancer detection.
• To investigate the role of tsRNAs in bladder cancer progression and regulation.
• To evaluate the diagnostic value of specific tsRNAs in plasma for bladder cancer.

Main Methods:

• Plasma tsRNA sequencing in bladder cancer patients and healthy controls.
• Bioinformatic analysis to identify differentially expressed tsRNAs.
• Validation of candidate tsRNAs using training and validation cohorts.
• In vitro and in vivo experiments to assess the functional role of tsRNAs in bladder cancer.

Main Results:

• Identified and validated two specific tsRNAs, tRF-1:28-chrM.Ser-TGA and tiRNA-1:34-Glu-CTC-1-M2, significantly upregulated in BLCA plasma.
• These tsRNAs demonstrated high diagnostic accuracy for BLCA in ROC analyses.
• Circulating tsRNAs were specifically released by BLCA cells and correlated with tumor malignancy.
• The identified tsRNAs exacerbated BLCA progression and influenced tumor lipid metabolism.

Conclusions:

• Plasma tRF-1:28-chrM.Ser-TGA and tiRNA-1:34-Glu-CTC-1-M2 are promising biomarkers for early bladder cancer screening and diagnosis.
• These tsRNAs may serve as novel molecular targets for bladder cancer treatment.
• The findings underscore the potential of tsRNAs as non-invasive diagnostic tools in oncology.