Analysis of the Applicability of microRNAs in Peripheral Blood Leukocytes as Biomarkers of Sensitivity and Exposure to Fractionated Radiotherapy towards Breast Cancer |
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Authors: | Michal Marczyk Joanna Polaska Andrzej Wojcik Lovisa Lundholm |
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Affiliation: | 1.Department of Data Science and Engineering, Silesian University of Technology, 44-100 Gliwice, Poland; (M.M.); (J.P.);2.Yale Cancer Center, Yale School of Medicine, New Haven, CT 06511, USA;3.Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden;4.Institute of Biology, Jan Kochanowski University, 25-406 Kielce, Poland |
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Abstract: | Biomarkers for predicting individual response to radiation and for dose verification are needed to improve radiotherapy. A biomarker should optimally show signal fidelity, meaning that its level is stable and proportional to the absorbed dose. miRNA levels in human blood serum were suggested as promising biomarkers. The aim of the present investigation was to test the miRNA biomarker in leukocytes of breast cancer patients undergoing external beam radiotherapy. Leukocytes were isolated from blood samples collected prior to exposure (control); on the day when a total dose of 2 Gy, 10 Gy, or 20 Gy was reached; and one month after therapy ended (46–50 Gy in total). RNA sequencing was performed and univariate analysis was used to analyse the effect of the radiation dose on the expression of single miRNAs. To check if combinations of miRNAs can predict absorbed dose, a multinomial logistic regression model was built using a training set from eight patients (representing 40 samples) and a validation set with samples from the remaining eight patients (15 samples). Finally, Broadside, an explorative interaction mining tool, was used to extract sets of interacting miRNAs. The most prominently increased miRNA was miR-744-5p, followed by miR-4461, miR-34a-5p, miR-6513-5p, miR-1246, and miR-454-3p. Decreased miRNAs were miR-3065-3p, miR-103a-2-5p, miR-30b-3p, and miR-5690. Generally, most miRNAs showed a relatively strong inter-individual variability and different temporal patterns over the course of radiotherapy. In conclusion, miR-744-5p shows promise as a stable miRNA marker, but most tested miRNAs displayed individual signal variability which, at least in this setting, may exclude them as sensitive biomarkers of radiation response. |
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Keywords: | miRNA radiation biomarker radiotherapy |
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