Circulating Micro-RNAs as Biomarkers for Thoracic Radiation Therapy in Lung Cancer

Risk of normal tissues toxicity limits the amount of thoracic radiation therapy that can be routinely prescribed for the treatment of non-small cell lung cancer (NSCLC). An early biomarker of response to thoracic radiation may provide a way to predict eventual toxicities during the multi-week treatment regimen. This enables dose adjustment before the symptomatic onset of late effects, such as radiation pneumonitis and esophagitis. Micro-RNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by decreasing the translation of messenger RNAs. miRNAs constitute a major fraction of small RNAs reproducibly found in circulation, in part due to their protective encapsulation within exosomes. They are therefore attractive candidates as serological biomarkers. In this study, we performed miRNA profiling of the blood of 5 NSCLC patients at 5 dose-points during thoracic RT and found 10 miRNAs that correlated well with total radiation dose as well as other common dosimetric parameters. We then assessed these 10 miRNAs in samples from a separate cohort of 21 NSCLC patients receiving RT and identified miR-29a-3p and miR-150-5p as potential, reproducible biomarkers that decreased in