American Association for Cancer Research
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Supplementary Data from miR-31-3p Expression and Benefit from Anti-EGFR Inhibitors in Metastatic Colorectal Cancer Patients Enrolled in the Prospective Phase II PROSPECT-C Trial

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journal contribution
posted on 2023-03-31, 20:40 authored by Gayathri Anandappa, Andrea Lampis, David Cunningham, Khurum H. Khan, Kyriakos Kouvelakis, Georgios Vlachogiannis, Somaieh Hedayat, Nina Tunariu, Sheela Rao, David Watkins, Naureen Starling, Chiara Braconi, Mahnaz Darvish-Damavandi, Hazel Lote, Janet Thomas, Clare Peckitt, Ria Kalaitzaki, Nasir Khan, Nicos Fotiadis, Massimo Rugge, Ruwaida Begum, Isma Rana, Annette Bryant, Jens C. Hahne, Ian Chau, Matteo Fassan, Nicola Valeri

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Funding

Cancer Research UK

NIHR

Royal Marsden NHS Foundation Trust

Institute of Cancer Research

FP7

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ARTICLE ABSTRACT

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. 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. 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). Our study validates the role of miR-31-3p as potential predictive biomarker of selection for anti-EGFR mAbs.

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