Long Interspersed Nuclear Element-1 Analytes in Extracellular Vesicles as Tools for Molecular Diagnostics of Non-Small Cell Lung Cancer

Aberrant expression of the oncogenic retrotransposon LINE-1 is a hallmark of various cancer types, including non-small cell lung cancers (NSCLCs). Here, we present proof-of-principle evidence that LINE-1 analytes in extracellular vesicles (EVs) serve as tools for molecular diagnostics of NSCLC, with LINE-1 status in tumor cells and tissues mirroring the LINE-1 mRNA and ORF1p cargos of EVs from lung cancer cell culture conditioned media or human plasma. The levels of LINE-1 analytes in plasma EVs from ostensibly healthy individuals were higher in females than males. While the profiles of LINE-1 mRNA and ORF1p in African Americans compared to Hispanics were not significantly different, African Americans showed slightly higher ORF1p content, and 2-3 times greater ranges of LINE-1 values compared to Hispanics. Whole plasma ORF1p levels correlated with EV ORF1p levels, indicating that most of the circulating LINE-1 protein is contained within EVs. EV LINE-1 mRNA levels were elevated in patients with advanced cancer stages and in select patients with squamous cell carcinoma and metastatic tumors compared to adenocarcinomas. The observed EV LINE-1 mRNA profiles paralleled the patterns of ORF1p expression in NSCLC tissue sections suggesting that LINE-1 analytes in plasma EVs may serve to monitor the activity of LINE-1 retroelements in lung cancer.