Author:
Quintanilha Julia C. F.,Cursino Maria A.,Borges Jessica B.,Torso Nadine G.,Bastos Larissa B.,Oliveira Juliana M.,Cobaxo Thiago S.,Pincinato Eder C.,Hirata Mario H.,Geraldo Murilo V.,Lima Carmen S. P.,Moriel Patricia
Abstract
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.
Funder
Fundação de Amparo à Pesquisa do Estado de São Paulo
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference32 articles.
1. Gold JM, Raja A. Cisplatin. [Updated 2020 May 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; Available online: https://www.ncbi.nlm.nih.gov/books/NBK547695/.
2. Siddik ZH. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene. 2003;22:7265–79.
3. Quintanilha JCF, Visacri MB, Sousa VM, Bastos LB, Vaz CO, Guarnieri JPO, et al. Cisplatin-induced human peripheral blood mononuclear cells’ oxidative stress and nephrotoxicity in head and neck cancer patients: the influence of hydrogen peroxide. Mol Cell Biochem. 2018;440:139–45.
4. Visacri MB, Pincinato EC, Ferrari GB, Quintanilha JCF, Mazzola PG, Lima CSP, et al. Adverse drug reactions and kinetics of cisplatin excretion in urine of patients undergoing cisplatin chemotherapy and radiotherapy for head and neck cancer: a prospective study. Daru. 2017;25:12.
5. Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of cisplatin nephrotoxicity. Toxins (Basel). 2010;2:2490–518.
Cited by
14 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献