High Expression of a tRNA^Pro Derivative Associates with Poor Survival and Independently Predicts Colorectal Cancer...

Colorectal cancer (CRC) is the second most lethal cause of cancer-related deaths in Europe. Fragments of tRNA^Pro are conserved among vertebrates, characterized by pleiotropic regulatory functions and have been found to discriminate colorectal tumors from normal colorectal mucosa. In the current study, we investigated the prognostic utility of 5'-tiRNA-Pro^TGG levels in CRC. For this purpose, total RNA was extracted from 155 malignant colorectal tumors and 74 adjacent non-cancerous tissue specimens, polyadenylated and reverse-transcribed using an oligo-dT adapter as primer. Real-time quantitative PCR (qPCR) was used to assess the levels of 5'-tiRNA-Pro^TGG. Kaplan-Meier survival analysis demonstrated that high 5'-tiRNA-Pro^TGG levels predict both poor disease-free survival (DFS) and overall survival (OS) of CRC patients. Of note, high 5'-tiRNA-Pro^TGG levels retain their unfavorable prognostic value in patients with rectal cancer and/or moderately differentiated CRC (grade II). More importantly, multivariate cox regression analysis highlighted that the overexpression of 5'-tiRNA-Pro^TGG constitutes an adverse prognostic factor predicting short-term relapse of CRC patients independently of the established prognosticators in CRC. Finally, bioinformatics analysis unveiled a potentially critical role of 5'-tiRNA-Pro^TGG regarding the maintenance of cellular homeostasis, signaling, cell communication, and cellular motility.