MiR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity in patients with head and neck cancer

Abstract Background No biomarker is available for identifying cancer patients at risk of developing nephrotoxicity when treated with cisplatin. Methods We performed microRNA (miRNA) sequencing using plasma collected 5 days after cisplatin treatment (D5) from twelve patients with head and neck cancer...

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Main Authors: Julia C. F. Quintanilha, Maria A. Cursino, Jessica B. Borges, Nadine G. Torso, Larissa B. Bastos, Juliana M. Oliveira, Thiago S. Cobaxo, Eder C. Pincinato, Mario H. Hirata, Murilo V. Geraldo, Carmen S. P. Lima, Patricia Moriel
Format: Article
Language:English
Published: BMC 2021-05-01
Series:BMC Cancer
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Online Access:https://doi.org/10.1186/s12885-021-08317-2
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author Julia C. F. Quintanilha
Maria A. Cursino
Jessica B. Borges
Nadine G. Torso
Larissa B. Bastos
Juliana M. Oliveira
Thiago S. Cobaxo
Eder C. Pincinato
Mario H. Hirata
Murilo V. Geraldo
Carmen S. P. Lima
Patricia Moriel
author_facet Julia C. F. Quintanilha
Maria A. Cursino
Jessica B. Borges
Nadine G. Torso
Larissa B. Bastos
Juliana M. Oliveira
Thiago S. Cobaxo
Eder C. Pincinato
Mario H. Hirata
Murilo V. Geraldo
Carmen S. P. Lima
Patricia Moriel
author_sort Julia C. F. Quintanilha
collection DOAJ
description Abstract Background No biomarker is available for identifying cancer patients at risk of developing nephrotoxicity when treated with cisplatin. Methods We performed microRNA (miRNA) sequencing using plasma collected 5 days after cisplatin treatment (D5) from twelve patients with head and neck cancer with and without nephrotoxicity (grade ≥ 2 increased serum creatinine). The most differentially expressed miRNAs between the two groups were selected for quantification at baseline and D5 in a larger cohort of patients. The association between miRNAs and nephrotoxicity was evaluated by calculating the odds ratio (OR) from univariate logistic regression. Receiver operating characteristic curves (ROC) were used to estimate the area under the curve (AUC), sensitivity, and specificity. Results MiR-3168 (p = 1.98 × 10− 8), miR-4718 (p = 4.24 × 10− 5), and miR-6125 (p = 6.60 × 10− 5) were the most differentially expressed miRNAs and were further quantified in 43, 48, and 53 patients, respectively. The baseline expression of miR-3168 (p = 0.0456, OR = 1.03, 95% CI: 1.00–1.06) and miR-4718 (p = 0.0388, OR = 1.56, 95% CI: 1.03–2.46) were associated with an increased risk of nephrotoxicity, whereas miR-6125 showed a trend (p = 0.0618, OR = 1.73, 95% CI: 0.98–3.29). MiR-4718 showed the highest AUC (0.77, 95% CI: 0.61–0.93) with sensitivity of 66.76 and specificity of 79.49. Conclusions We have provided evidence of baseline plasmatic expression of miR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity.
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spelling doaj.art-beff4f2334684d0c87b0a669cb60c8e32022-12-21T21:58:43ZengBMCBMC Cancer1471-24072021-05-0121111010.1186/s12885-021-08317-2MiR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity in patients with head and neck cancerJulia C. F. Quintanilha0Maria A. Cursino1Jessica B. Borges2Nadine G. Torso3Larissa B. Bastos4Juliana M. Oliveira5Thiago S. Cobaxo6Eder C. Pincinato7Mario H. Hirata8Murilo V. Geraldo9Carmen S. P. Lima10Patricia Moriel11School of Medical Science, University of CampinasSchool of Medical Science, University of CampinasDante Pazzanese Institute of CardiologyFaculty of Pharmaceutical Sciences, University of CampinasFaculty of Pharmaceutical Sciences, University of CampinasFaculty of Pharmaceutical Sciences, University of CampinasFaculty of Pharmaceutical Sciences, University of CampinasSchool of Medical Science, University of CampinasDante Pazzanese Institute of CardiologyInstitute of Biology, University of CampinasSchool of Medical Science, University of CampinasSchool of Medical Science, University of CampinasAbstract Background No biomarker is available for identifying cancer patients at risk of developing nephrotoxicity when treated with cisplatin. Methods We performed microRNA (miRNA) sequencing using plasma collected 5 days after cisplatin treatment (D5) from twelve patients with head and neck cancer with and without nephrotoxicity (grade ≥ 2 increased serum creatinine). The most differentially expressed miRNAs between the two groups were selected for quantification at baseline and D5 in a larger cohort of patients. The association between miRNAs and nephrotoxicity was evaluated by calculating the odds ratio (OR) from univariate logistic regression. Receiver operating characteristic curves (ROC) were used to estimate the area under the curve (AUC), sensitivity, and specificity. Results MiR-3168 (p = 1.98 × 10− 8), miR-4718 (p = 4.24 × 10− 5), and miR-6125 (p = 6.60 × 10− 5) were the most differentially expressed miRNAs and were further quantified in 43, 48, and 53 patients, respectively. The baseline expression of miR-3168 (p = 0.0456, OR = 1.03, 95% CI: 1.00–1.06) and miR-4718 (p = 0.0388, OR = 1.56, 95% CI: 1.03–2.46) were associated with an increased risk of nephrotoxicity, whereas miR-6125 showed a trend (p = 0.0618, OR = 1.73, 95% CI: 0.98–3.29). MiR-4718 showed the highest AUC (0.77, 95% CI: 0.61–0.93) with sensitivity of 66.76 and specificity of 79.49. Conclusions We have provided evidence of baseline plasmatic expression of miR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity.https://doi.org/10.1186/s12885-021-08317-2CisplatinNephrotoxicitymicroRNAsmiR-3168miR-6125miR-4718
spellingShingle Julia C. F. Quintanilha
Maria A. Cursino
Jessica B. Borges
Nadine G. Torso
Larissa B. Bastos
Juliana M. Oliveira
Thiago S. Cobaxo
Eder C. Pincinato
Mario H. Hirata
Murilo V. Geraldo
Carmen S. P. Lima
Patricia Moriel
MiR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity in patients with head and neck cancer
BMC Cancer
Cisplatin
Nephrotoxicity
microRNAs
miR-3168
miR-6125
miR-4718
title MiR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity in patients with head and neck cancer
title_full MiR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity in patients with head and neck cancer
title_fullStr MiR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity in patients with head and neck cancer
title_full_unstemmed MiR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity in patients with head and neck cancer
title_short MiR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity in patients with head and neck cancer
title_sort mir 3168 mir 6125 and mir 4718 as potential predictors of cisplatin induced nephrotoxicity in patients with head and neck cancer
topic Cisplatin
Nephrotoxicity
microRNAs
miR-3168
miR-6125
miR-4718
url https://doi.org/10.1186/s12885-021-08317-2
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