(M1330-04-26) Urinary MicroRNAs as Possible Biomarkers of Cisplatin-Induced Nephrotoxicity in Patients with Head and Neck Cancer

Purpose: Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent cancers worldwide [1], and its standard treatment is cisplatin-based chemoradiotherapy. One of the main adverse reactions of this treatment is nephrotoxicity, for which there is currently no adequate specific and sensitive biomarker [2]. MicroRNAs (miRNAs), a class of non-coding RNAs, are among the most promising candidates for the development of renal biomarkers, particularly due to their distinct expression patterns in different tissues or pathological states, as well as their stability in various biofluids [3,4]. Therefore, this study aimed to evaluate the potential use of urinary microRNAs (miRNAs) as candidate biomarkers for renal damage.

Methods: This was a retrospective cohort study. Nephrotoxicity was assessed by analyzing blood samples collected before and five days (D5) after chemotherapy administration. Variations in biomarker values from the baseline were graded for severity according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 4 [5]. The Risk, Injury, Failure, Loss, and End-Stage Kidney Disease (RIFLE) [6] and Acute Kidney Injury Network (AKIN) [7] criteria were used to classify cases of acute kidney injury (AKI). MiRNAs were extracted from urine samples collected at baseline and D5, and the expression of six miRNAs was assessed using RT-qPCR. Relative expression was evaluated using the 2-∆Ct method. A significance level of 5% was adopted.

Results: A total of 49 participants were included (n = 49), divided into two groups: a group of participants without cisplatin-induced nephrotoxicity (n = 25) and a group of participants with nephrotoxicity (n = 24). Significant differences were observed between the two groups in terms of traditional renal markers (serum creatinine and creatinine clearance) and the classification of acute kidney injury (AKI). Among the six miRNAs assessed, 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). However, only hsa-miR-6805-5p showed a significant difference in expression between the two groups of participants (p < 0.0001). The receiver operating characteristic (ROC) curve for this miRNA demonstrated excellent specificity (0.920) in assessing its expression fluctuation, while its absolute expression at D5 showed higher sensitivity (0.792) (Figure 1). Therefore, the integrated use of these two parameters appears to be a promising approach for identifying cases of AKI.

Conclusion: Among head and neck cancer patients treated with cisplatin, hsa-miR-6805-5p has shown promise as a potential biomarker for cisplatin-induced nephrotoxicity. The findings of this study encourage further research on this miRNA to better understand its value as a biomarker.

References: 1. Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA. Cancer J. Clin. 2021, 71, 209–249, doi:10.3322/caac.21660.
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Acknowledgements: 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 2019/13250-1, 2017/02338-0 and 2019/20010-7 . The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the University of Campinas (protocol code: 65397517.7.0000.5404, February 8, 2021).

Figure 1: Receiver operating characteristic (ROC) curve of hsa-miR-6805-5p. On the left, ROC curve of its expression five days (D5) after cisplatin administration, and on the right, considering the variation in expression between D5 and baseline.