High Expression of a tRNA<sup>Pro</sup> Derivative Associates with Poor Survival and Independently Predicts Colorectal Cancer Recurrence

Colorectal cancer (CRC) is the second most lethal cause of cancer-related deaths in Europe. Fragments of tRNA<sup>Pro</sup> are conserved among vertebrates, characterized by pleiotropic regulatory functions and have been found to discriminate colorectal tumors from normal colorectal muco...

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Main Authors: Panagiotis Tsiakanikas, Panagiotis G. Adamopoulos, Dimitra Tsirba, Pinelopi I. Artemaki, Iordanis N. Papadopoulos, Christos K. Kontos, Andreas Scorilas
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/5/1120
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author Panagiotis Tsiakanikas
Panagiotis G. Adamopoulos
Dimitra Tsirba
Pinelopi I. Artemaki
Iordanis N. Papadopoulos
Christos K. Kontos
Andreas Scorilas
author_facet Panagiotis Tsiakanikas
Panagiotis G. Adamopoulos
Dimitra Tsirba
Pinelopi I. Artemaki
Iordanis N. Papadopoulos
Christos K. Kontos
Andreas Scorilas
author_sort Panagiotis Tsiakanikas
collection DOAJ
description Colorectal cancer (CRC) is the second most lethal cause of cancer-related deaths in Europe. Fragments of tRNA<sup>Pro</sup> 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<sup>TGG</sup> 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<sup>TGG</sup>. Kaplan-Meier survival analysis demonstrated that high 5′-tiRNA-Pro<sup>TGG</sup> levels predict both poor disease-free survival (DFS) and overall survival (OS) of CRC patients. Of note, high 5′-tiRNA-Pro<sup>TGG</sup> 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<sup>TGG</sup> 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<sup>TGG</sup> regarding the maintenance of cellular homeostasis, signaling, cell communication, and cellular motility.
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spelling doaj.art-fcc4d410ad5a4491a6877065e05051a62023-11-23T10:11:20ZengMDPI AGBiomedicines2227-90592022-05-01105112010.3390/biomedicines10051120High Expression of a tRNA<sup>Pro</sup> Derivative Associates with Poor Survival and Independently Predicts Colorectal Cancer RecurrencePanagiotis Tsiakanikas0Panagiotis G. Adamopoulos1Dimitra Tsirba2Pinelopi I. Artemaki3Iordanis N. Papadopoulos4Christos K. Kontos5Andreas Scorilas6Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, GreeceDepartment of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, GreeceDepartment of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, GreeceDepartment of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, GreeceFourth Surgery Department, National and Kapodistrian University of Athens, University General Hospital “Attikon”, 12462 Athens, GreeceDepartment of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, GreeceDepartment of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, GreeceColorectal cancer (CRC) is the second most lethal cause of cancer-related deaths in Europe. Fragments of tRNA<sup>Pro</sup> 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<sup>TGG</sup> 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<sup>TGG</sup>. Kaplan-Meier survival analysis demonstrated that high 5′-tiRNA-Pro<sup>TGG</sup> levels predict both poor disease-free survival (DFS) and overall survival (OS) of CRC patients. Of note, high 5′-tiRNA-Pro<sup>TGG</sup> 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<sup>TGG</sup> 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<sup>TGG</sup> regarding the maintenance of cellular homeostasis, signaling, cell communication, and cellular motility.https://www.mdpi.com/2227-9059/10/5/1120tRNA-derived small RNA (tsRNA)tRNA-derived fragment (tRF)tRNA halfmolecular tumor biomarkersprognosiscolon carcinoma
spellingShingle Panagiotis Tsiakanikas
Panagiotis G. Adamopoulos
Dimitra Tsirba
Pinelopi I. Artemaki
Iordanis N. Papadopoulos
Christos K. Kontos
Andreas Scorilas
High Expression of a tRNA<sup>Pro</sup> Derivative Associates with Poor Survival and Independently Predicts Colorectal Cancer Recurrence
Biomedicines
tRNA-derived small RNA (tsRNA)
tRNA-derived fragment (tRF)
tRNA half
molecular tumor biomarkers
prognosis
colon carcinoma
title High Expression of a tRNA<sup>Pro</sup> Derivative Associates with Poor Survival and Independently Predicts Colorectal Cancer Recurrence
title_full High Expression of a tRNA<sup>Pro</sup> Derivative Associates with Poor Survival and Independently Predicts Colorectal Cancer Recurrence
title_fullStr High Expression of a tRNA<sup>Pro</sup> Derivative Associates with Poor Survival and Independently Predicts Colorectal Cancer Recurrence
title_full_unstemmed High Expression of a tRNA<sup>Pro</sup> Derivative Associates with Poor Survival and Independently Predicts Colorectal Cancer Recurrence
title_short High Expression of a tRNA<sup>Pro</sup> Derivative Associates with Poor Survival and Independently Predicts Colorectal Cancer Recurrence
title_sort high expression of a trna sup pro sup derivative associates with poor survival and independently predicts colorectal cancer recurrence
topic tRNA-derived small RNA (tsRNA)
tRNA-derived fragment (tRF)
tRNA half
molecular tumor biomarkers
prognosis
colon carcinoma
url https://www.mdpi.com/2227-9059/10/5/1120
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