Transfer RNA-Derived Small RNAs: Novel Predictive Biomarkers for Diagnosis and Prognosis of Breast Cancer.

tRNA-derived small RNAs (tsRNAs) have emerged as important regulators in cancer biology, yet their role in breast cancer remains insufficiently understood. This study identifies tRF-30-PW5SVP9N15WV as a tsRNA consistently upregulated in breast cancer, supported by analyses of TCGA-BRCA and independent clinical cohorts. Elevated expression was an independent predictor of poor overall survival (HR = 20.83, 95% CI 2.76-157.35; p < 0.001) and displayed superior prognostic power compared with TNM stage. A nomogram integrating tRF-30-PW5SVP9N15WV achieved a C-index of 0.78, with time-dependent ROC AUCs of 0.882, 0.733, 0.704, and 0.662 at 1, 3, 5, and 10 years, respectively, outperforming clinical parameters alone. Functional assays demonstrated that tRF-30-PW5SVP9N15WV promotes proliferation (CCK-8, colony formation) and invasion (Transwell migration) in vitro, while xenograft and tail-vein injection models confirmed its ability to accelerate tumor growth and lung metastasis (p < 0.01) in vivo. Subcellular fractionation revealed predominant cytoplasmic localization (67.1%), consistent with posttranscriptional regulatory activity. Clinically, tRF-30-PW5SVP9N15WV also exhibited diagnostic potential in differentiating malignant from benign tissues (AUC = 0.805). Together, these findings establish tRF-30-PW5SVP9N15WV as a clinically relevant tsRNA with diagnostic, prognostic, and therapeutic relevance in breast cancer.