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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Date
2019-07-01ICR Author
Author
Anandappa, G
Lampis, A
Cunningham, D
Khan, KH
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, JC
Chau, I
Fassan, M
Valeri, N
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Subject
Humans
Colorectal Neoplasms
MicroRNAs
Tomography, X-Ray Computed
Prognosis
Treatment Outcome
Retreatment
Immunohistochemistry
In Situ Hybridization
Gene Expression
Aged
Middle Aged
Female
Male
Molecular Targeted Therapy
ErbB Receptors
Biomarkers, Tumor
Antineoplastic Agents, Immunological
Research team
Signal Transduction & Molecular Pharmacology
Gastrointestinal Cancers Clinical Trials
Medicine (RMH Smith Cunningham)
Evolutionary Genomics & Modelling
Functional Genomics
Gastrointestinal Cancer Biology and Genomics
Language
eng
Date accepted
2019-03-26
License start date
2019-07
Citation
Clinical cancer research : an official journal of the American Association for Cancer Research, 2019, 25 (13), pp. 3830 - 3838
Publisher
AMER ASSOC CANCER RESEARCH