TY - JOUR
T1 - MicroRNA signature in metastatic colorectal cancer patients treated with anti-EGFR monoclonal antibodies
AU - Cappuzzo, Federico
AU - Sacconi, Andrea
AU - Landi, Lorenza
AU - Ludovini, Vienna
AU - Biagioni, Francesca
AU - D'Incecco, Armida
AU - Capodanno, Alessandra
AU - Salvini, Jessica
AU - Corgna, Enrichetta
AU - Cupini, Samanta
AU - Barbara, Cecilia
AU - Fontanini, Gabriella
AU - Crinò, Lucio
AU - Blandino, Giovanni
PY - 2014
Y1 - 2014
N2 - Background To investigate whether microRNAs are predictive of sensitivity to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies in patients with metastatic colorectal cancer (mCRC). Methods A total of 183 mCRC cases from 2 independent cohorts (cohort 1: 74 cases; validation cohort: 109 cases) treated with cetuximab or panitumumab were included in the study. MiRNA arrays were analyzed using Agilent's miRNA platform. Results The study identified the cluster Let-7c/miR-99a/miR-125b as a signature associated with an outcome different from that of anti-EGFR therapies. In the first cohort, patients with high-intensity signatures had a significantly longer progression-free survival (PFS) (6.1 vs. 2.3 mo; P =.02) and longer overall survival (OS) (29.8 vs. 7.0 mo, P =.08) than patients with low-intensity signatures. In the validation cohort, patients with high signature had significantly longer PFS and OS than individuals with low-intensity signatures (PFS 7.8 vs. 4.3 mo, P =.02; OS 12.8 vs. 7.5 mo, P =.02). In the KRAS wild-type population (n = 120), high-intensity signature patients had a significantly longer PFS (7.8 vs. 4.6 mo, P =.016) and longer OS (16.1 vs. 10.9 mo, P =.09) than low-signature individuals, with no difference in KRAS mutated patients. Conclusion The MiR-99a/Let-7c/miR-125b signature may improve the selection of patients with KRAS wild-type mCRC as good candidates for anti-EGFR therapy.
AB - Background To investigate whether microRNAs are predictive of sensitivity to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies in patients with metastatic colorectal cancer (mCRC). Methods A total of 183 mCRC cases from 2 independent cohorts (cohort 1: 74 cases; validation cohort: 109 cases) treated with cetuximab or panitumumab were included in the study. MiRNA arrays were analyzed using Agilent's miRNA platform. Results The study identified the cluster Let-7c/miR-99a/miR-125b as a signature associated with an outcome different from that of anti-EGFR therapies. In the first cohort, patients with high-intensity signatures had a significantly longer progression-free survival (PFS) (6.1 vs. 2.3 mo; P =.02) and longer overall survival (OS) (29.8 vs. 7.0 mo, P =.08) than patients with low-intensity signatures. In the validation cohort, patients with high signature had significantly longer PFS and OS than individuals with low-intensity signatures (PFS 7.8 vs. 4.3 mo, P =.02; OS 12.8 vs. 7.5 mo, P =.02). In the KRAS wild-type population (n = 120), high-intensity signature patients had a significantly longer PFS (7.8 vs. 4.6 mo, P =.016) and longer OS (16.1 vs. 10.9 mo, P =.09) than low-signature individuals, with no difference in KRAS mutated patients. Conclusion The MiR-99a/Let-7c/miR-125b signature may improve the selection of patients with KRAS wild-type mCRC as good candidates for anti-EGFR therapy.
KW - Cetuximab
KW - Let-7c
KW - miR-125b
KW - miR-99a
KW - Panitumumab
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U2 - 10.1016/j.clcc.2013.11.006
DO - 10.1016/j.clcc.2013.11.006
M3 - Article
C2 - 24503111
AN - SCOPUS:84893210980
VL - 13
JO - Clinical Colorectal Cancer
JF - Clinical Colorectal Cancer
SN - 1533-0028
IS - 1
ER -