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Identification of miR-499a-5p as a Potential Novel Biomarker for Risk Stratification in Endometrial Cancer

INTRODUCTION: The Cancer Genome Atlas (TCGA) project identified four distinct prognostic groups in endometrial cancer (EC), among which two are correlated with an intermediate prognosis: the MisMatch Repair-deficient (MMRd) and the No Specific Molecular Profile (NSMP) groups. The two groups represen...

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Autores principales: Ravegnini, Gloria, De Leo, Antonio, Coada, Camelia, Gorini, Francesca, de Biase, Dario, Ceccarelli, Claudio, Dondi, Giulia, Tesei, Marco, De Crescenzo, Eugenia, Santini, Donatella, Corradini, Angelo Gianluca, Tallini, Giovanni, Hrelia, Patrizia, De Iaco, Pierandrea, Angelini, Sabrina, Perrone, Anna Myriam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597024/
https://www.ncbi.nlm.nih.gov/pubmed/34804952
http://dx.doi.org/10.3389/fonc.2021.757678
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author Ravegnini, Gloria
De Leo, Antonio
Coada, Camelia
Gorini, Francesca
de Biase, Dario
Ceccarelli, Claudio
Dondi, Giulia
Tesei, Marco
De Crescenzo, Eugenia
Santini, Donatella
Corradini, Angelo Gianluca
Tallini, Giovanni
Hrelia, Patrizia
De Iaco, Pierandrea
Angelini, Sabrina
Perrone, Anna Myriam
author_facet Ravegnini, Gloria
De Leo, Antonio
Coada, Camelia
Gorini, Francesca
de Biase, Dario
Ceccarelli, Claudio
Dondi, Giulia
Tesei, Marco
De Crescenzo, Eugenia
Santini, Donatella
Corradini, Angelo Gianluca
Tallini, Giovanni
Hrelia, Patrizia
De Iaco, Pierandrea
Angelini, Sabrina
Perrone, Anna Myriam
author_sort Ravegnini, Gloria
collection PubMed
description INTRODUCTION: The Cancer Genome Atlas (TCGA) project identified four distinct prognostic groups in endometrial cancer (EC), among which two are correlated with an intermediate prognosis: the MisMatch Repair-deficient (MMRd) and the No Specific Molecular Profile (NSMP) groups. The two groups represent a heterogeneous subset of patients frequently harboring CTNNB1 alterations with distinctive clinicopathologic features. The study aimed to evaluate the miRNA expression in ECs to identify potential biomarkers of prognosis. METHODS: We analyzed miRNA expression in 72 ECs classified as MMRd or NSMP including 15 ECs with CTNNB1 mutations. In the discovery step, miRNA expression was evaluated in 30 cases through TaqMan miRNA arrays. Subsequently, four miRNAs were validated in the total cohort of ECs. The data were further tested in the TCGA cohort, and correlations with overall survival (OS) and progression-free interval (PFI) were evaluated. RESULTS: miR-499a-3p and miR-499a-5p resulted to be overexpressed in CTNNB1 mutant EC patients at intermediate risk. Similarly, in the TCGA cohort, miR-499a-3p and miR-499a-5p were differentially expressed between CTNNB1 mutant and wild-type patients (p < 0.0001). NSMP patients with low miR-499a-5p expression showed longer OS (p = 0.03, log-rank test). By combining miR-499a-3p or -5p expression levels with the CTNNB1 status, ECs with CTNNB1 mutation and lower miR-499a-5p expression showed better OS compared with the other subgroups (p = 0.03, log-rank test), among the NSMP patients. Moreover, in a multivariate analysis, combination of wild type CTNNB1 status and high miR-499a-5p expression was indipendently associated with high risk of death [HR (95%CI): 3.53 (1.1-10.5), p = 0.02]. CONCLUSION: Our results suggest that the combination of CTNNB1 status and miR-499a-5p allows a better stratification of NSMP patients and could promote a personalization of the treatment in intermediate-risk patients.
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spelling pubmed-85970242021-11-18 Identification of miR-499a-5p as a Potential Novel Biomarker for Risk Stratification in Endometrial Cancer Ravegnini, Gloria De Leo, Antonio Coada, Camelia Gorini, Francesca de Biase, Dario Ceccarelli, Claudio Dondi, Giulia Tesei, Marco De Crescenzo, Eugenia Santini, Donatella Corradini, Angelo Gianluca Tallini, Giovanni Hrelia, Patrizia De Iaco, Pierandrea Angelini, Sabrina Perrone, Anna Myriam Front Oncol Oncology INTRODUCTION: The Cancer Genome Atlas (TCGA) project identified four distinct prognostic groups in endometrial cancer (EC), among which two are correlated with an intermediate prognosis: the MisMatch Repair-deficient (MMRd) and the No Specific Molecular Profile (NSMP) groups. The two groups represent a heterogeneous subset of patients frequently harboring CTNNB1 alterations with distinctive clinicopathologic features. The study aimed to evaluate the miRNA expression in ECs to identify potential biomarkers of prognosis. METHODS: We analyzed miRNA expression in 72 ECs classified as MMRd or NSMP including 15 ECs with CTNNB1 mutations. In the discovery step, miRNA expression was evaluated in 30 cases through TaqMan miRNA arrays. Subsequently, four miRNAs were validated in the total cohort of ECs. The data were further tested in the TCGA cohort, and correlations with overall survival (OS) and progression-free interval (PFI) were evaluated. RESULTS: miR-499a-3p and miR-499a-5p resulted to be overexpressed in CTNNB1 mutant EC patients at intermediate risk. Similarly, in the TCGA cohort, miR-499a-3p and miR-499a-5p were differentially expressed between CTNNB1 mutant and wild-type patients (p < 0.0001). NSMP patients with low miR-499a-5p expression showed longer OS (p = 0.03, log-rank test). By combining miR-499a-3p or -5p expression levels with the CTNNB1 status, ECs with CTNNB1 mutation and lower miR-499a-5p expression showed better OS compared with the other subgroups (p = 0.03, log-rank test), among the NSMP patients. Moreover, in a multivariate analysis, combination of wild type CTNNB1 status and high miR-499a-5p expression was indipendently associated with high risk of death [HR (95%CI): 3.53 (1.1-10.5), p = 0.02]. CONCLUSION: Our results suggest that the combination of CTNNB1 status and miR-499a-5p allows a better stratification of NSMP patients and could promote a personalization of the treatment in intermediate-risk patients. Frontiers Media S.A. 2021-10-29 /pmc/articles/PMC8597024/ /pubmed/34804952 http://dx.doi.org/10.3389/fonc.2021.757678 Text en Copyright © 2021 Ravegnini, De Leo, Coada, Gorini, de Biase, Ceccarelli, Dondi, Tesei, De Crescenzo, Santini, Corradini, Tallini, Hrelia, De Iaco, Angelini and Perrone https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Ravegnini, Gloria
De Leo, Antonio
Coada, Camelia
Gorini, Francesca
de Biase, Dario
Ceccarelli, Claudio
Dondi, Giulia
Tesei, Marco
De Crescenzo, Eugenia
Santini, Donatella
Corradini, Angelo Gianluca
Tallini, Giovanni
Hrelia, Patrizia
De Iaco, Pierandrea
Angelini, Sabrina
Perrone, Anna Myriam
Identification of miR-499a-5p as a Potential Novel Biomarker for Risk Stratification in Endometrial Cancer
title Identification of miR-499a-5p as a Potential Novel Biomarker for Risk Stratification in Endometrial Cancer
title_full Identification of miR-499a-5p as a Potential Novel Biomarker for Risk Stratification in Endometrial Cancer
title_fullStr Identification of miR-499a-5p as a Potential Novel Biomarker for Risk Stratification in Endometrial Cancer
title_full_unstemmed Identification of miR-499a-5p as a Potential Novel Biomarker for Risk Stratification in Endometrial Cancer
title_short Identification of miR-499a-5p as a Potential Novel Biomarker for Risk Stratification in Endometrial Cancer
title_sort identification of mir-499a-5p as a potential novel biomarker for risk stratification in endometrial cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597024/
https://www.ncbi.nlm.nih.gov/pubmed/34804952
http://dx.doi.org/10.3389/fonc.2021.757678
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