miR-6805-5p as a biomarker of cisplatin-induced nephrotoxicity in patients with head and neck cancer

Nadine De Godoy Torso; Julia Coelho França Quintanilha; Maria Aparecida Cursino; Eder De Carvalho Pincinato; Pía Loren; Luis A Salazar; Carmen Silvia Passos Lima; Patricia Moriel

doi:10.3389/fphar.2023.1275238

miR-6805-5p as a biomarker of cisplatin-induced nephrotoxicity in patients with head and neck cancer

Front Pharmacol. 2023 Nov 28:14:1275238. doi: 10.3389/fphar.2023.1275238. eCollection 2023.

Authors

Nadine De Godoy Torso¹, Julia Coelho França Quintanilha¹, Maria Aparecida Cursino¹, Eder De Carvalho Pincinato¹, Pía Loren², Luis A Salazar², Carmen Silvia Passos Lima¹, Patricia Moriel³

Affiliations

¹ School of Medical Sciences, Universidade Estadual de Campinas, Campinas, Brazil.
² Center of Molecular Biology and Pharmacogenetics, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, Temuco, Chile.
³ Faculty of Pharmaceutical Sciences, Universidade Estadual de Campinas, Campinas, Brazil.

Abstract

Introduction: The standard treatment for head and neck squamous cell carcinoma (HNSCC) is cisplatin chemoradiotherapy. One of the main treatment adverse reactions is nephrotoxicity, for which there is currently no adequate specific and sensitive biomarker. Thus, this study aimed to evaluate the use of microRNAs (miRNAs) as renal biomarker candidates. Methods: This was a retrospective cohort study. Nephrotoxicity was assessed through blood samples collected before and 5 days (D5) after chemotherapy. MiRNAs were extracted from urine samples collected at baseline and D5, and RNA sequencing identified miRNAs differentially expressed between participants with and without cisplatin-induced nephrotoxicity. Results: A total of 49 participants were included (n = 49). A significant difference was seen between the two groups for traditional renal markers (serum creatinine and creatinine clearance) and for the acute kidney injury (AKI) categories. Among the six miRNAs evaluated as biomarkers, four were upregulated (hsa-miR-6729-5p, hsa-miR-1238-5p, hsa-miR-4706, and hsa-miR-4322) and two were downregulated (hsa-miR-6805-5p and hsa-miR-21-5p), but only hsa-miR-6805-5p had a significant difference (p < 0.0001). Its receiver operating characteristic curve revealed excellent specificity (0.920) for its expression fluctuation assessment, while its absolute expression in D5 showed greater sensitivity (0.792). Conclusion: So, the integrated use of these two parameters seems to be an interesting approach for AKI.

Keywords: acute kidney injury; biomarker; cisplatin; miRNA; microRNA; nephrotoxicity.

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES) (Finance Code 001) and by the São Paulo Research Foundation (FAPESP), grant numbers 2017/02338-0, 2019/20010-7, and 2019/13250-1. The content of this article results from the Pharmaceutical Security Nucleus Project, object of Agreement No. 895688/2019, the result of a partnership between the Ministry of Justice and Public Security of Brazil, through the Fund for the Defense of Diffuse Rights, and the State University of Campinas. Said content does not necessarily reflect the official position of the Ministry or the Fund on the subject under consideration.