소세포폐암 유래 exosomal miRNAs을 활용한 진단 및 예후 예측

Abstract

Small cell lung cancer (SCLC), an aggressive lung tumor with a poor prognosis, has a problem that there are many somatic cell mutations, causes metastatic diseases, and is difficult to diagnose early. Cancer-derived exosomal miRNAs are considered as stable and non-invasive biomarkers for diagnosis and prognosis. Therefore, early detection of SCLC by using exosomal miRNAs can be critical to improving clinical outcomes. We investigated the miRNA of exosomes secreted from serum in 5 normal patients and 5 SCLC patients using microarray-based expression profiling. In the result of miRNA array, we found out highly expressed 15 miRNAs that are validated in large cohort consist of 76 SCLC patients. In comparison to the levels in 50 healthy volunteers, miR-3656, miR-3124-5p, 200b-3p, miR-6515, miR-9-5p, miR-3126-3p are highly expressed in SCLC serum samples. Moreover, among them, exosomal miR-3124-5p, miR-6515-5p and miR-9-5p indicate high expression of both limited disease (LD) and extended disease (ED) in SCLC although there was no exosomal miRNA with a significant difference in overall survival. In addition, functional enrichment analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that Ras signaling pathway and RNA polymerase II transcription involved in miRNA mechanisms. These results suggest that highly expressed exosomal miRNAs in patient serum can be utilized as potential diagnostic biomarkers.