Whole Transcriptome Profiling of Liquid Biopsies from Tumour Xenografted Mouse Models Enables Specific Monitoring of Tumour-derived Extracellular RNA

Overview

Journal NAR Cancer

Publisher Oxford University Press

Specialty Oncology

Date 2022 Dec 1

PMID 36451702

Authors

Vanessa Vermeirssen

Jill Deleu

Annelien Morlion

Celine Everaert

Jilke De Wilde

Jasper Anckaert

Kaat Durinck

Justine Nuytens

Muhammad Rishfi

Frank Speleman

Hanne Van Droogenbroeck

Kimberly Verniers

Maria Francesca Baietti

Maarten Albersen

Eleonora Leucci

Edward Post

Myron G Best

Tom Van Maerken

Bram De Wilde

Jo Vandesompele

Anneleen Decock

Affiliations

Soon will be listed here.

Abstract

While cell-free DNA (cfDNA) is widely being investigated, free circulating RNA (extracellular RNA, exRNA) has the potential to improve cancer therapy response monitoring and detection due to its dynamic nature. However, it remains unclear in which blood subcompartment tumour-derived exRNAs primarily reside. We developed a host-xenograft deconvolution framework, exRNAxeno, with mapping strategies to either a combined human-mouse reference genome or both species genomes in parallel, applicable to exRNA sequencing data from liquid biopsies of human xenograft mouse models. The tool enables to distinguish (human) tumoural RNA from (murine) host RNA, to specifically analyse tumour-derived exRNA. We applied the combined pipeline to total exRNA sequencing data from 95 blood-derived liquid biopsy samples from 30 mice, xenografted with 11 different tumours. Tumoural exRNA concentrations are not determined by plasma platelet levels, while host exRNA concentrations increase with platelet content. Furthermore, a large variability in exRNA abundance and transcript content across individual mice is observed. The tumoural gene detectability in plasma is largely correlated with the RNA expression levels in the tumour tissue or cell line. These findings unravel new aspects of tumour-derived exRNA biology in xenograft models and open new avenues to further investigate the role of exRNA in cancer.

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