Transcriptomic Profiling of Plasma Extracellular Vesicles Enables Reliable Annotation of the Cancer-Specific Transcriptome and Molecular Subtype

Authors

Vahid Bahrambeigi
Jaewon J Lee
Vittorio Branchi
Kimal I Rajapakshe
Zhichao Xu
Naishu Kui
Jason T Henry
Wang Kun
Bret M Stephens
Sarah Dhebat
Mark W Hurd
Ryan Sun
Peng Yang
Eytan Ruppin
Wenyi Wang
Scott Kopetz
Anirban Maitra
Paola A Guerrero

Publication Date

5-15-2024

Journal

Cancer Research

Abstract

Longitudinal monitoring of patients with advanced cancers is crucial to evaluate both disease burden and treatment response. Current liquid biopsy approaches mostly rely on the detection of DNA-based biomarkers. However, plasma RNA analysis can unleash tremendous opportunities for tumor state interrogation and molecular subtyping. Through the application of deep learning algorithms to the deconvolved transcriptomes of RNA within plasma extracellular vesicles (evRNA), we successfully predicted consensus molecular subtypes in patients with metastatic colorectal cancer. Analysis of plasma evRNA also enabled monitoring of changes in transcriptomic subtype under treatment selection pressure and identification of molecular pathways associated with recurrence. This approach also revealed expressed gene fusions and neoepitopes from evRNA. These results demonstrate the feasibility of using transcriptomic-based liquid biopsy platforms for precision oncology approaches, spanning from the longitudinal monitoring of tumor subtype changes to the identification of expressed fusions and neoantigens as cancer-specific therapeutic targets, sans the need for tissue-based sampling.

Significance: The development of an approach to interrogate molecular subtypes, cancer-associated pathways, and differentially expressed genes through RNA sequencing of plasma extracellular vesicles lays the foundation for liquid biopsy-based longitudinal monitoring of patient tumor transcriptomes.

Keywords

Humans, Extracellular Vesicles, Transcriptome, Gene Expression Profiling, Biomarkers, Tumor, Liquid Biopsy, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Neoplasms

DOI

10.1158/0008-5472.CAN-23-4070

PMID

38451249

PMCID

PMC11096054

PubMedCentral® Posted Date

11-15-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes