Monitoring lung cancer response to therapy via exosomal miRNA profiling

Abstract

Treatment for lung cancers can be difficult due to the aggressive nature of the disease and the current challenge posed by the expensive, invasive, and potentially unreliable monitoring of therapy response via computed tomography (CT) scans. In recent years, blood exosomal miRNA has been used to search for diagnostic and prognostic biomarkers and suggests an interesting potential alternative monitoring method through blood sampling as a form of "liquid biopsy". In small studies, miRNAs have previously demonstrated prognostic value in cancer patients receiving a given therapy; however, the value of serial blood exosomal miRNA profiling in assessing treatment response has not been well studied. Through the use of exosomes extracted from the blood plasma of 45 lung cancer patients and TaqMan Array PCR miRNA analysis, we show a panel of four exosomal miRNAs that may be beneficial in determining treatment response in lung cancer patients. Exosomal miRNAs miR-181c-3p, miR-500a-3p, miR-99a-5p, and miR-10b-5p were significantly upregulated in the lung cancer cohort before treatment as compared to controls, and miR-181c-3p was significantly downregulated after treatment. However, we were unable to detect a correlation between changes in exosomal miRNA profiles post treatment and clinical response to therapy, in part due to the small size of the study and the challenges of assessing response to therapy using CT scans. This study has provided the groundwork for further evaluation of an exosomal miRNA panel to monitor treatment response in advanced lung cancer. The study has also generated hypotheses regarding miRNA families as lung cancer biomarkers, to be further investigated.