MicroRNAs as possible biomarkers of cisplatin-induced nephrotoxicity in patients with head and neck cancer

Author(s)

Nadine de Godoy Torso

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2022-07-15

Examining board members

Patricia Moriel; Cláudia Vianna Maurer Morelli; Patrícia de Carvalho Mastroianni

• Advisor: Patricia Moriel

Abstract

The recommended treatment for advanced stages of head and neck cancer (HNC) consists of radiotherapy concomitant with chemotherapy with cisplatin; however, its use is limited due to adverse reactions, especially nephrotoxicity. Since classical markers have low sensitivity and specificity, there is a need to identify new biomarkers of nephrotoxicity. Among those proposed in recent years, one of the most promising is microRNA (miRNA). Therefore, the aim of this study was to evaluate miRNAs as possible biomarkers of cisplatin-induced nephrotoxicity in patients with HNC. This is a retrospective, cohort study. Patients with HNC who underwent antineoplastic treatment with cisplatin (80-100mg/m2 every 21 days, for 3 cycles; only the 1st cycle was considered for the analysis) concomitant with radiotherapy were included. Nephrotoxicity was evaluated according to severity according to Common Terminology Criteria for Adverse Events version 4.3, and acute kidney injury (AKI) according to AKIN (Acute Kidney Injury Network) and RIFLE (Risk, Injury, Failure, Loss, and End-stage) classifications. kidney disease). Based on the conduct of a systematic literature review and on previous next-generation sequencing results, 6 miRNAs (hsa-miR-6729-5p, hsa-miR-1238-5p, hsa-miR-4706, hsa-miR-6805-5p, hsa-miR-4322 and hsa-miR-21-5p) to have their expression validated by RT-qPCR, before and 5 days after chemotherapy, in urine samples. The analysis of these results was performed only for those participants who had a consensus regarding their renal function by both the RIFLE and AKIN classifications. Comparison of the expression profile of these miRNAs between groups with (n = 24) and without renal adverse drug reaction (ADR) (n = 25) was evaluated by the 2-?CT method. After treatment, it was observed that there was a statistically significant change for almost all nephrotoxicity markers, mainly accentuated on the fifth day after chemotherapy (D5). With the exception of hsa-miR-6729-5p (basal - p = 0.3284, D5 - p = 0.2625) and hsa-miR-4706 (basal - p = 0.1170, D5 - p = 0.0733 ), all others showed a tendency towards higher expression in the group without renal before and after chemotherapy (hsa-miR-1238-5p baseline - p = 0.1170, D5 - p = 0.0733; hsa-miR-6805- 5p basal - p = 0.6519, D5 - p = 0.3582; hsa-miR-4322 basal - p = 0.8237, D5 - p = 0.6271; hsa-miR-21-5p basal - p = 0.3479, D5 - p = 0.0801). According to the Receiver Operating Characteristic curve, hsa-miR-1238-5p showed high sensitivity (1.000) and hsa-miR-21-5p the highest specificity between the two (0.640). These results should be evaluated in new clinical studies with a greater number of patients, so that they can possibly help the clinician in the choice and follow-up of the chemotherapy treatment for these patients (AU)

• FAPESP's process: 19/20010-7 - MicroRNAs as possible cypplin-induced nephrotoxicity predictors in head and neck cancer patients
• Grantee: Nadine de Godoy Torso
• Support Opportunities: Scholarships in Brazil - Master