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

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 predict consensus molecular subtypes in metastatic colorectal cancer patients. We further demonstrate the ability to monitor changes in transcriptomic subtype under treatment selection pressure and identify molecular pathways in evRNA associated with recurrence. Our approach also identified expressed gene fusions and neoepitopes from evRNA. These results demonstrate the feasibility of transcriptomic-based liquid biopsy platforms for precision oncology approaches, spanning from the longitudinal monitoring of tumor subtype changes to identification of expressed fusions and neoantigens as cancer-specific therapeutic targets, sans the need for tissue-based sampling.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - year:2024

Enthalten in:

Cancer research - (2024) vom: 07. März

Sprache:

Englisch

Beteiligte Personen:

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

Links:

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Themen:

Journal Article

Anmerkungen:

Date Revised 17.04.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.1158/0008-5472.CAN-23-4070

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369410173