Exploratory analysis of miRNAs-21, -26a, -34a, -181c, -181d, and -485-5p as potential biomarkers for tumor treating fields sensitivity in primary glioblastoma cell cultures

Tumor Treating Fields (TTFields) are approved for glioblastoma (GBM) treatment, but predictive biomarkers remain unclear. This study evaluates TTFields effectiveness in primary GBM cell cultures and explores miRNA biomarkers in tumor tissue, plasma, and primary cell cultures. TTFields were applied to 21 primary GBM cell cultures for 72 h. Cell viability was assessed pre- and post-treatment, with parallel evaluations in control cultures. Expression levels of miRNAs-21, -26a, -34a, -181c, -181d, and -485-5p were analyzed in tumor tissue, plasma, and untreated/treatment-exposed cultures. Correlation analyses examined TTFields response and miRNA expression. Response rates varied, with a mean cell viability reduction of 48.53%. Expression of miRNA-26a in tumor tissue (p = 0.041, r = 0.502) and miRNAs-21, -26a, and -181c in untreated control cultures (p < 0.05) correlated with increased TTFields effectiveness. Linear correlations were observed for miRNAs-26a and -181c in untreated control cultures ([95% CI: 0.001938-0.01725, p = 0.016; 95% CI: 0.0000003935-0.0001641, p = 0.049). Individual GBM cell cultures respond differently to TTFields. Overexpression of miRNA-26a in native tumor tissue and overexpression of miRNAs-21, -26a and -181c in untreated control cell cultures were positively correlated with increased effectiveness of TTFields treatment.