BS49 Cardiac injury microrna profile in breast cancer patients treated with left-sided radiotherapy

Introduction Radiotherapy (RT) for breast cancer may cause incidental radiation exposure to the heart, leading to radiation-related cardiac disease. Early detection of subclinical cardiotoxicity is a challenge due to the limited sensitivity and specificity of clinical screening tests. Currently, miRNAs are under investigation for use as biomarkers. This project focussed on evaluating the expression levels of circulating cardiac-injury associated miRNAs in RT-treated left-sided breast cancer patients. Methods Plasma samples from 32 breast cancer patients treated with left-sided RT (incidental mean whole heart dose 1.40±0.61 Gy) were analysed at 5 time points: Baseline and post-RT (i.e. 24–72 hours, 3–6 months, 6–12 months, and 5 years post-RT). Global miRNA was extracted from pooled plasma samples and analysed using the TaqMan Array Human MicroRNA A cards (Life Technologies). The key differentially altered miRNAs associated with cardiac injury development were validated by quantitative PCR using individual patient samples. The differential expression of intracellular pathway mechanisms correlated with the miRNA expression signature was performed using the Ingenuity Pathway Analysis (IPA) software (Qiagen). Results Profiling of pooled plasma samples from the array study revealed differential expression of 22 miRNAs associated with cardiac injuries at the post-RT time points compared to baseline. The validation analysis of the candidate miRNAs showed that 17 miRNAs (miR-1, miR-122, miR-125a-5p, miR-130a, miR-133a, miR-133b, miR-150, miR-186, miR-197, miR-21, miR-221, miR-222, miR-223, miR-27a, miR-30b, miR-30c and miR-320a) were significantly downregulated 24–72 hours post-RT. From these, 8 miRNAs remained downregulated at 3–6 and 6–12 months post-RT time points (figure 1). The IPA Core Analysis revealed that the miRNAs altered post-RT (i.e. 24–72 hours, 3–6 months, 6–12 months) compared to baseline were associated with angiogenesis, vasculogenesis, inflammatory response, vascular lesion, and cardiac lesion (figure 2). Conclusions The results from this study demonstrate that radiation exposure significantly altered the expression levels of key cardiac injury-associated miRNAs in breast cancer patients. Furthermore, modulation of these miRNA expression levels could be associated with the development of cardiovascular pathologies post-RT. The validation of individual patient samples with key miRNA targets may enable their expression levels to be related to individual variations in cardiac dose. The identified miRNA panel could potentially be used as biomarkers to screen cancer patients for cardiac injury at an early stage. Conflict of Interest No conflict of interest