High Expression of a tRNAPro Derivative Associates with Poor Survival and Independently Predicts Colorectal Cancer Recurrence

Panagiotis Tsiakanikas; Panagiotis G Adamopoulos; Dimitra Tsirba; Pinelopi I Artemaki; Iordanis N Papadopoulos; Christos K Kontos; Andreas Scorilas

doi:10.3390/biomedicines10051120

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

Biomedicines. 2022 May 12;10(5):1120. doi: 10.3390/biomedicines10051120.

Authors

Panagiotis Tsiakanikas¹, Panagiotis G Adamopoulos¹, Dimitra Tsirba¹, Pinelopi I Artemaki¹, Iordanis N Papadopoulos², Christos K Kontos¹, Andreas Scorilas¹

Affiliations

¹ Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, Greece.
² Fourth Surgery Department, National and Kapodistrian University of Athens, University General Hospital "Attikon", 12462 Athens, Greece.

Abstract

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.

Keywords: colon cancer progression; colon carcinoma; functional in silico analysis; molecular tumor biomarkers; prognosis; real-time quantitative PCR (qPCR); survival; tRNA half; tRNA-derived fragment (tRF); tRNA-derived small RNA (tsRNA).

Grants and funding

This research received no external funding.