Hsa-miR-210-3p expression in breast cancer and its putative association with worse outcome in patients treated with Docetaxel

Barbara Pasculli, Raffaela Barbano, Michelina Rendina, Andrea Fontana, Massimiliano Copetti, Tommaso Mazza, Vanna Maria Valori, Maria Morritti, Evaristo Maiello, Paolo Graziano, Roberto Murgo, Vito Michele Fazio, Manel Esteller, Paola Parrella

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Abstract

MicroRNA-210-3p is the most prominent hypoxia regulated microRNA, and it has been found significantly overexpressed in different human cancers. We performed the expression analysis of miR-210-3p in a retrospective cohort of breast cancer patients with a median follow-up of 76 months (n = 283). An association between higher levels of miR-210-3p and risk of disease progression (HR: 2.13, 95%CI: 1.33-3.39, P = 0.002) was found in the subgroup of patients treated with Epirubicin and Cyclophosphamide followed by Docetaxel. Moreover, a cut off value of 20.966 established by ROC curve analyses allowed to discriminate patients who developed distant metastases with an accuracy of 85% at 3- (AUC: 0.870, 95%CI: 0.690-1.000) and 83% at 5-years follow up (AUC: 0.832, 95%CI: 0.656–1.000). Whereas the accuracy in discriminating patients who died for the disease was of 79.6% at both 5- (AUC: 0.804, 95%CI: 0.517–1.000) and 10-years (AUC: 0.804. 95%CI: 0.517–1.000) follow-up. In silico analysis of miR-210-3p and Docetaxel targets provided evidence for a putative molecular cross-talk involving microtubule regulation, drug efflux metabolism and oxidative stress response. Overall, our data point to the miR-210-3p involvement in the response to therapeutic regimens including Docetaxel in sequential therapy with anthracyclines, suggesting it may represent a predictive biomarker in breast cancer patients.

Original languageEnglish
Article number14913
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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docetaxel
Area Under Curve
Breast Neoplasms
MicroRNAs
ROC Curve
Epirubicin
Drug and Narcotic Control
Anthracyclines
Microtubules
Computer Simulation
Cyclophosphamide
Disease Progression
Oxidative Stress
Biomarkers
human MIRN210 microRNA
Neoplasm Metastasis

ASJC Scopus subject areas

  • General

Cite this

@article{3244f9c7130148a587b9e0934e9bba4c,
title = "Hsa-miR-210-3p expression in breast cancer and its putative association with worse outcome in patients treated with Docetaxel",
abstract = "MicroRNA-210-3p is the most prominent hypoxia regulated microRNA, and it has been found significantly overexpressed in different human cancers. We performed the expression analysis of miR-210-3p in a retrospective cohort of breast cancer patients with a median follow-up of 76 months (n = 283). An association between higher levels of miR-210-3p and risk of disease progression (HR: 2.13, 95{\%}CI: 1.33-3.39, P = 0.002) was found in the subgroup of patients treated with Epirubicin and Cyclophosphamide followed by Docetaxel. Moreover, a cut off value of 20.966 established by ROC curve analyses allowed to discriminate patients who developed distant metastases with an accuracy of 85{\%} at 3- (AUC: 0.870, 95{\%}CI: 0.690-1.000) and 83{\%} at 5-years follow up (AUC: 0.832, 95{\%}CI: 0.656–1.000). Whereas the accuracy in discriminating patients who died for the disease was of 79.6{\%} at both 5- (AUC: 0.804, 95{\%}CI: 0.517–1.000) and 10-years (AUC: 0.804. 95{\%}CI: 0.517–1.000) follow-up. In silico analysis of miR-210-3p and Docetaxel targets provided evidence for a putative molecular cross-talk involving microtubule regulation, drug efflux metabolism and oxidative stress response. Overall, our data point to the miR-210-3p involvement in the response to therapeutic regimens including Docetaxel in sequential therapy with anthracyclines, suggesting it may represent a predictive biomarker in breast cancer patients.",
author = "Barbara Pasculli and Raffaela Barbano and Michelina Rendina and Andrea Fontana and Massimiliano Copetti and Tommaso Mazza and Valori, {Vanna Maria} and Maria Morritti and Evaristo Maiello and Paolo Graziano and Roberto Murgo and Fazio, {Vito Michele} and Manel Esteller and Paola Parrella",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41598-019-51581-3",
language = "English",
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T1 - Hsa-miR-210-3p expression in breast cancer and its putative association with worse outcome in patients treated with Docetaxel

AU - Pasculli, Barbara

AU - Barbano, Raffaela

AU - Rendina, Michelina

AU - Fontana, Andrea

AU - Copetti, Massimiliano

AU - Mazza, Tommaso

AU - Valori, Vanna Maria

AU - Morritti, Maria

AU - Maiello, Evaristo

AU - Graziano, Paolo

AU - Murgo, Roberto

AU - Fazio, Vito Michele

AU - Esteller, Manel

AU - Parrella, Paola

PY - 2019/12/1

Y1 - 2019/12/1

N2 - MicroRNA-210-3p is the most prominent hypoxia regulated microRNA, and it has been found significantly overexpressed in different human cancers. We performed the expression analysis of miR-210-3p in a retrospective cohort of breast cancer patients with a median follow-up of 76 months (n = 283). An association between higher levels of miR-210-3p and risk of disease progression (HR: 2.13, 95%CI: 1.33-3.39, P = 0.002) was found in the subgroup of patients treated with Epirubicin and Cyclophosphamide followed by Docetaxel. Moreover, a cut off value of 20.966 established by ROC curve analyses allowed to discriminate patients who developed distant metastases with an accuracy of 85% at 3- (AUC: 0.870, 95%CI: 0.690-1.000) and 83% at 5-years follow up (AUC: 0.832, 95%CI: 0.656–1.000). Whereas the accuracy in discriminating patients who died for the disease was of 79.6% at both 5- (AUC: 0.804, 95%CI: 0.517–1.000) and 10-years (AUC: 0.804. 95%CI: 0.517–1.000) follow-up. In silico analysis of miR-210-3p and Docetaxel targets provided evidence for a putative molecular cross-talk involving microtubule regulation, drug efflux metabolism and oxidative stress response. Overall, our data point to the miR-210-3p involvement in the response to therapeutic regimens including Docetaxel in sequential therapy with anthracyclines, suggesting it may represent a predictive biomarker in breast cancer patients.

AB - MicroRNA-210-3p is the most prominent hypoxia regulated microRNA, and it has been found significantly overexpressed in different human cancers. We performed the expression analysis of miR-210-3p in a retrospective cohort of breast cancer patients with a median follow-up of 76 months (n = 283). An association between higher levels of miR-210-3p and risk of disease progression (HR: 2.13, 95%CI: 1.33-3.39, P = 0.002) was found in the subgroup of patients treated with Epirubicin and Cyclophosphamide followed by Docetaxel. Moreover, a cut off value of 20.966 established by ROC curve analyses allowed to discriminate patients who developed distant metastases with an accuracy of 85% at 3- (AUC: 0.870, 95%CI: 0.690-1.000) and 83% at 5-years follow up (AUC: 0.832, 95%CI: 0.656–1.000). Whereas the accuracy in discriminating patients who died for the disease was of 79.6% at both 5- (AUC: 0.804, 95%CI: 0.517–1.000) and 10-years (AUC: 0.804. 95%CI: 0.517–1.000) follow-up. In silico analysis of miR-210-3p and Docetaxel targets provided evidence for a putative molecular cross-talk involving microtubule regulation, drug efflux metabolism and oxidative stress response. Overall, our data point to the miR-210-3p involvement in the response to therapeutic regimens including Docetaxel in sequential therapy with anthracyclines, suggesting it may represent a predictive biomarker in breast cancer patients.

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