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

Author:

Bowers Emma C.1,Cavalcante Alexandre M.2ORCID,Nguyen Kimberly1,Li Can1,Wang Yingshan1,El-Zein Randa3,Chen Shu-Hsia3,Kim Min P.3,McKay Brian S.4ORCID,Ramos Kenneth S.13

Affiliation:

1. Texas A&M Institute of Biosciences and Technology, Center for Genomic and Precision Medicine, Houston, TX 77030, USA

2. Department of Medicine, University of Arizona College of Medicine—Tucson, Tucson, AZ 85721, USA

3. Houston Methodist Hospital Cancer Center and the Houston Methodist Academic Institute, Houston, TX 77030, USA

4. Department of Ophthalmology, University of Arizona College of Medicine—Tucson, Tucson, AZ 85721, USA

Abstract

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.

Funder

University of Arizona Bio5 Postdoctoral Fellowship

Texas Governors Distinguished Research Investigator Award

2020 Houston Methodist Research Institute Cancer Center Innovative Award

Texas A&M University Presidential Award

Publisher

MDPI AG

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