Association between microRNAs 10b/21/34a and acute toxicity in glioblastoma patients treated with radiotherapy and temozolomide

Abstract

A personalized approach to chemoradiation is important in reducing its potential side effects and identifying a group of patients prone to toxicity. MicroRNAs have been shown to have a predictive potential for radiotoxicity. The goal of the study was to test if levels of miRNA in peripheral blood mononuclear cells of glioblastoma patients are associated with toxicity and to identify the peak time point for toxicity. MicroRNA-10b/21/34a levels were measured in 43 patients with and without toxicity, at baseline, at the 15th, and at the 30th fraction by Real-Time quantitative Polymerase Chain Reaction. MicroRNA-10b/21 levels increased with toxicity grade (p = 0.014; p = 0.013); miR-21/34a levels were significantly different between patients with and without toxicity at the 15th fraction (p = 0.030; p = 0.045), while miR-34a levels significantly changed during treatment (p < 0.001). All three miRNAs showed a significantly high positive correlation with one another. MiR-34a might be considered as a predictive factor for toxicity due to its changes during treatment, and differences between the groups with and without toxicity; miR-10b might be used to predict toxicity; miR-10b/21 might be used for predicting the grade of toxicity in GB patients.

Figure 1

Grade of toxicity over time during treatment with RT and TMZ. “No toxicity” represents patients at baseline, before treatment. It does not represent grade. The grade of toxicity was defined as 1, 2, 3, and 4 (in our cohort there were no patients with grade 4 toxicity, although the maximal grade according to CTCAE ver.5.0 scoring is 4). *According to CTCAE ver. 5.0 grade 5 (death) is not adequate for some adverse events and therefore was not an option.

Figure 2

Comparison between patients with and without side effects at the 15th fraction of RT. Violet dots represent each patient, while the black line represents the median value of miR-10b (a) and miR-34a (b) expression values (RQ relative quantity units) at each analyzed group-with and without side effects at the 15th fraction-15f).

Figure 3

Changes of miR-10b/21/34a over time during the treatment. Violet dots represent each patient, while the black line represents the median value of expression (RQ relative quantity units) for miR-10b (a-without toxicity, and d-with toxicity), miR-21 (b-without toxicity, and e-with toxicity), and miR-34a (c-without toxicity, and f-with toxicity).