To assess the clinical significance of tRF biomarkers for PCa, the present study selected common 5′tRFs differentially expressed in PCa tissue from different high throughput small RNA studies [19,20,22,23] and validated their use in semen samples from men with moderately altered serum PSA levels, where the identification of truly non-invasive biomarkers of PCa is more necessary. This evidence concerns the gene KLK3 and posterior cortical atrophy.