miR-31-3p expression and benefit from anti-EGFR inhibitors in metastatic colorectal cancer patients enrolled in the prospective phase II PROSPECT-C trial

Anandappa, G. et al. (2019) miR-31-3p expression and benefit from anti-EGFR inhibitors in metastatic colorectal cancer patients enrolled in the prospective phase II PROSPECT-C trial. Clinical Cancer Research, 25(13), pp. 3830-3838. (doi: 10.1158/1078-0432.ccr-18-3769) (PMID:30952636)

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Abstract

Purpose: Anti-EGFR mAbs are effective in the treatment of metastatic colorectal cancer (mCRC) patients. RAS status and tumor location (sidedness) are predictive markers of patients' response to anti-EGFR mAbs. Recently, low miR-31-3p expression levels have been correlated with clinical benefit from the anti-EGFR mAb cetuximab. Here, we aimed to validate the predictive power of miR-31-3p in a prospective cohort of chemorefractory mCRC patients treated with single-agent anti-EGFR mAbs. Experimental Design: miR-31-3p was tested by in situ hybridization (ISH) in 91 pretreatment core biopsies from metastatic deposits of 45 patients with mCRC. Sequential tissue biopsies obtained before treatment, at the time of partial response, and at disease progression were tested to monitor changes in miR-31-3p expression overtreatment. miR-31-3p expression, sidedness, and RAS status in pretreatment cell-free DNA were combined in multivariable regression models to assess the predictive value of each variable alone or in combination. Results: Patients with low miR-31-3p expression in pretreatment biopsies showed better overall response rate, as well as better progression-free survival and overall survival, compared to those with high miR-31-3p expression. The prognostic effect of miR-31-3p was independent from age, gender, and sidedness. No significant changes in the expression of miR-31-3p were observed when sequential tissue biopsies were tested in long-term or poor responders to anti-EGFR mAbs. miR-31-3p scores were similar when pretreatment biopsies were compared with treatment-naïve archival tissues (often primary colorectal cancer). Conclusions: Our study validates the role of miR-31-3p as potential predictive biomarker of selection for anti-EGFR mAbs.

Item Type:Articles
Additional Information:This work was supported by Cancer Research UK (grant number CEA A18052), the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research (grant numbers A62, A100, A101, A159), and the European Union FP7 (grant number CIG 334261) to N. Valeri. The authors acknowledge support from the National Institute for Health Research Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Valeri, Dr Nicola and Braconi, Dr Chiara
Authors: Anandappa, G., Lampis, A., Cunningham, D., Khan, K. H., Kouvelakis, K., Vlachogiannis, G., Hedayat, S., Tunariu, N., Rao, S., Watkins, D., Starling, N., Braconi, C., Darvish-Damavandi, M., Lote, H., Thomas, J., Peckitt, C., Kalaitzaki, R., Khan, N., Fotiadis, N., Rugge, M., Begum, R., Rana, I., Bryant, A., Hahne, J. C., Chau, I., Fassan, M., and Valeri, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Clinical Cancer Research
Publisher:American Association for Cancer Research
ISSN:1078-0432
ISSN (Online):1557-3265
Published Online:05 April 2019
Copyright Holders:Copyright © 2019 American Association for Cancer Research
First Published:First published in Clinical Cancer Research 25(13):3830-3838
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
629721TamiRCRT - Targeting microRNAs for ColoRectal Cancer TherapyNicola ValeriEuropean Commission (EC)334261RI CANCER SCIENCES