Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Circulating Tumour Cell Associated MicroRNA Profiles Change during Chemoradiation and are Predictive of Response in Locally Advanced Rectal Cancer

Stephanie H Lim
* ORCID logo ,
Wei Chua
,
Weng Ng
,
Emilia Ip
,
Tania M Marques
,
Nham T Tran
,
Margarida Gama-Carvalho
,
Ray Asghari
,
Christopher Henderson
,
Yafeng Ma
ORCID logo ,
Paul De Souza
,
Kevin J. Spring
ORCID logo
Version 1 : Received: 23 June 2023 / Approved: 26 June 2023 / Online: 26 June 2023 (14:09:03 CEST)

A peer-reviewed article of this Preprint also exists.

Lim, S.H.; Chua, W.; Ng, W.; Ip, E.; Marques, T.M.; Tran, N.T.; Gama-Carvalho, M.; Asghari, R.; Henderson, C.; Ma, Y.; de Souza, P.; Spring, K.J. Circulating Tumour Cell Associated MicroRNA Profiles Change during Chemoradiation and Are Predictive of Response in Locally Advanced Rectal Cancer. Cancers 2023, 15, 4184. Lim, S.H.; Chua, W.; Ng, W.; Ip, E.; Marques, T.M.; Tran, N.T.; Gama-Carvalho, M.; Asghari, R.; Henderson, C.; Ma, Y.; de Souza, P.; Spring, K.J. Circulating Tumour Cell Associated MicroRNA Profiles Change during Chemoradiation and Are Predictive of Response in Locally Advanced Rectal Cancer. Cancers 2023, 15, 4184.

Abstract

Locally advanced rectal cancer (LARC) has traditionally been treated with trimodality therapy consisting of neoadjuvant radiation +/- chemotherapy, surgery and adjuvant chemotherapy. There is currently a clinical need for biomarkers to predict treatment response and outcomes, especially during neoadjuvant therapy. Liquid biopsy in the form of circulating tumour cells (CTCs) and circulating nucleic acids in particular microRNAs (miRNA) are novel, highly stable and clinically relevant regulators of disease. We studied a prospective cohort of 52 patients with LARC, and obtained samples at baseline, during treatment, and post-treatment. We enumerated CTCs during chemoradiation at these three time-points, using the IsofluxTM CTC Isolation and detection platform. We then subjected the isolated CTCs to miRNA expression analyses, using a panel of 106 miRNA candidates. We identified CTCs in 73% of patients at baseline, and numbers fell during treatment and miRNA expression profiles also changed during treatment. Between baseline and during treatment (week 3) time-points three microRNAs (hsa-miR-95, hsa-miR-10a and hsa-miR-16-1*) were highly differentially expressed. Importantly, hsa-miR-19b-3p and hsa-miR-483-5p were found to correlate with good response to treatment. The latter (hsa-miR-483-5p) was also found to be differentially expressed between good responders and poor responders. They represent potential predictive biomarkers and a potential miRNA-based treatment strategy. In this study, we demonstrate that CTCs are present and can be isolated in the non-metastatic early stage cancer setting, and their associated miRNA profiles can potentially be utilized to predict treatment response.

Keywords

Locally advanced rectal cancer; chemoradiotherapy; microRNA; circulating tumour cells; lymphocytes; predictive biomarkers.

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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