Selective enrichment of plasma cell-free messenger RNA in cancer-associated extracellular vesicles.

Autor: Kim HJ; Cancer Early Detection Advanced Research Center (CEDAR), Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.; Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA., Rames MJ; Cancer Early Detection Advanced Research Center (CEDAR), Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.; Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA., Goncalves F; Cancer Early Detection Advanced Research Center (CEDAR), Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.; Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA., Kirschbaum CW; Cancer Early Detection Advanced Research Center (CEDAR), Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA., Roskams-Hieter B; Cancer Early Detection Advanced Research Center (CEDAR), Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA., Spiliotopoulos E; Cancer Early Detection Advanced Research Center (CEDAR), Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA., Briand J; Cancer Early Detection Advanced Research Center (CEDAR), Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA., Doe A; Cancer Early Detection Advanced Research Center (CEDAR), Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA., Estabrook J; Cancer Early Detection Advanced Research Center (CEDAR), Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.; Computational Biology Program, Oregon Health and Science University, Portland, OR, USA., Wagner JT; Cancer Early Detection Advanced Research Center (CEDAR), Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.; Molecular Genomics Laboratory, Providence Health and Services, Portland, OR, USA., Demir E; Cancer Early Detection Advanced Research Center (CEDAR), Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.; Computational Biology Program, Oregon Health and Science University, Portland, OR, USA.; Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA., Mills G; Division of Oncological Sciences, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA., Ngo TTM; Cancer Early Detection Advanced Research Center (CEDAR), Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA. ngth@ohsu.edu.; Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA. ngth@ohsu.edu.; Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA. ngth@ohsu.edu.; Division of Oncological Sciences, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA. ngth@ohsu.edu.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2023 Aug 29; Vol. 6 (1), pp. 885. Date of Electronic Publication: 2023 Aug 29.
DOI: 10.1038/s42003-023-05232-z
Abstrakt: Extracellular vesicles (EVs) have been shown as key mediators of extracellular small RNA transport. However, carriers of cell-free messenger RNA (cf-mRNA) in human biofluids and their association with cancer remain poorly understood. Here, we performed a transcriptomic analysis of size-fractionated plasma from lung cancer, liver cancer, multiple myeloma, and healthy donors. Morphology and size distribution analysis showed the successful separation of large and medium particles from other soluble plasma protein fractions. We developed a strategy to purify and sequence ultra-low amounts of cf-mRNA from particle and protein enriched subpopulations with the implementation of RNA spike-ins to control for technical variability and to normalize for intrinsic drastic differences in cf-mRNA amount carried in each plasma fraction. We found that the majority of cf-mRNA was enriched and protected in EVs with remarkable stability in RNase-rich environments. We observed specific enrichment patterns of cancer-associated cf-mRNA in each particle and protein enriched subpopulation. The EV-enriched differentiating genes were associated with specific biological pathways, such as immune systems, liver function, and toxic substance regulation in lung cancer, liver cancer, and multiple myeloma, respectively. Our results suggest that dissecting the complexity of EV subpopulations illuminates their biological significance and offers a promising liquid biopsy approach.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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