Integration of the whole proteome and transcriptome reveals a strong correlation between the protein and mRNA in a distinct population of cancer-derived EVs

ABSTRACT: Extracellular vesicles (EVs) are particles of different sizes, covered by a lipid bilayer membrane and containing highly heterogeneous cargo. Cancer cell-derived EVs have been the main object of an extensive investigation in the field because they carry cancer-specific molecular cargo and can promote cancer progression. Cancer-derived EVs include populations of atypically large EVs (L-EVs) that can be pelleted by a low/medium speed centrifugation, which have been referred to as tumor microvesicles, large oncosomes, or simply L-EVs. While small EVs (S-EVs), which pellet at a high speed centrifugation and include exosomes, have been investigated by a plethora of reports, little is known about the cargo of L-EVs. The paucity of studies comparing protein cargo of L- and S-EVs, of studies focused on protein coding RNA, and the absence of integrative analyses to compare the protein and gene expression in different EV fractions, prompted us to perform mass spectrometry to profile three different, size-based EV fractions generated by three cancer cell models (glioma, prostate and breast cancer). We identified general as well as cancer type-specific protein signatures for L- and S-EVs. A subset of the proteins enriched in prostate cancer cell-derived L-EVs was also identified in L-EVs from plasma of patients with metastatic prostate cancer by an independent Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH) mass spectrometry analysis. Proteomic and transcriptomic analyses of the prostate cancer-derived EVs revealed an enrichment of mitochondrial functions in L-EVs versus S-EVs at both the protein and RNA level. The mitochondrial signature was confirmed in L-EVs by single EV RNA-Seq. The integrated L-EV proteomic and transcriptomic signature enabled distinction between benign and localized prostate cancer, as well as between localized cancer and metastatic castration-resistant cancer.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Prostate Adenocarcinoma

SUBMITTER: Sarah Parker  

LAB HEAD: Doloros DiVisio

PROVIDER: PXD038011 | Pride | 2025-04-16

REPOSITORIES: Pride