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Clin Colorectal Cancer. 2014 Mar;13(1):37-45.e4. doi: 10.1016/j.clcc.2013.11.006. Epub 2013 Nov 14.

MicroRNA signature in metastatic colorectal cancer patients treated with anti-EGFR monoclonal antibodies.

Author information

1
Department of Medical Oncology, Civil Hospital of Livorno, Istituto Toscano Tumori, Livorno, Italy. Electronic address: f.cappuzzo@gmail.com.
2
Translational Oncogenomic Unit, National Cancer Institute Regina Elena, Rome, Italy.
3
Department of Medical Oncology, Civil Hospital of Livorno, Istituto Toscano Tumori, Livorno, Italy.
4
S.C. Oncologia Medica, Ospedale Santa Maria della Misericordia, Perugia, Italy.
5
Azienda Ospedaliera Universitaria Pisana, U.O. Anatomia ed Istologia Patologica III Universitaria, Pisa, Italy.

Abstract

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.

KEYWORDS:

Cetuximab; Let-7c; Panitumumab; miR-125b; miR-99a

PMID:
24503111
DOI:
10.1016/j.clcc.2013.11.006
[Indexed for MEDLINE]

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