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

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

doi:10.1158/0008-5472.CAN-23-4070

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

Journal article

Peer reviewed

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

Vahid Bahrambeigi, Jaewon J Lee, Vittorio Branchi, Kimal I Rajapakshe, Zhichao Xu, Naishu Kui, Jason T Henry, Wang Kun, Bret M Stephens, Sarah Dhebat, …

Cancer research (Chicago, Ill.), Vol.84(10), pp.1719-1732

05/15/2024

DOI: 10.1158/0008-5472.CAN-23-4070

PMID: 38451249

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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. 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.

Biomarkers, Tumor - blood

Biomarkers, Tumor - genetics

Colorectal Neoplasms - blood

Colorectal Neoplasms - genetics

Colorectal Neoplasms - pathology

Extracellular Vesicles - genetics

Extracellular Vesicles - metabolism

Gene Expression Profiling - methods

Gene Expression Regulation, Neoplastic

Humans

Liquid Biopsy - methods

Neoplasms - blood

Neoplasms - genetics

Neoplasms - pathology

Transcriptome

Details

Title: Subtitle: Transcriptomic Profiling of Plasma Extracellular Vesicles Enables Reliable Annotation of the Cancer-Specific Transcriptome and Molecular Subtype
Creators: Vahid Bahrambeigi - The University of Texas MD Anderson Cancer Center
Jaewon J Lee - Cedars-Sinai Medical Center
Vittorio Branchi - The University of Texas MD Anderson Cancer Center
Kimal I Rajapakshe - The University of Texas MD Anderson Cancer Center
Zhichao Xu - The University of Texas MD Anderson Cancer Center
Naishu Kui - The University of Texas MD Anderson Cancer Center
Jason T Henry - The University of Texas MD Anderson Cancer Center
Wang Kun - Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
Bret M Stephens - The University of Texas MD Anderson Cancer Center
Sarah Dhebat - The University of Texas MD Anderson Cancer Center
Mark W Hurd - The University of Texas MD Anderson Cancer Center
Ryan Sun - The University of Texas MD Anderson Cancer Center
Peng Yang - Rice University
Eytan Ruppin - National Cancer Institute
Wenyi Wang - The University of Texas MD Anderson Cancer Center
Scott Kopetz - The University of Texas MD Anderson Cancer Center
Anirban Maitra - The University of Texas MD Anderson Cancer Center
Paola A Guerrero - The University of Texas MD Anderson Cancer Center
Resource Type: Journal article
Publication Details: Cancer research (Chicago, Ill.), Vol.84(10), pp.1719-1732
DOI: 10.1158/0008-5472.CAN-23-4070
PMID: 38451249
ISSN: 0008-5472
eISSN: 1538-7445
Grant note: P50 CA221707 / NCI NIH HHS P30CA016672 / National Cancer Institute (NCI) R01CA218230 / National Cancer Institute (NCI) R01CA239342 / National Cancer Institute (NCI) R01CA268380 / National Cancer Institute (NCI) P50CA221707 / National Cancer Institute (NCI) T32CA009599 / National Cancer Institute (NCI) R01 CA268380 / NCI NIH HHS P30 CA016672 / NCI NIH HHS T32 CA009599 / NCI NIH HHS
Language: English
Date published: 05/15/2024
Academic Unit: Surgery
Record Identifier: 9985240987502771

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