title: MicroRNA signature in metastatic colorectal cancer patients treated with anti-EGFR monoclonal antibodies.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Medical Oncology, Civil Hospital of Livorno, Istituto Toscano Tumori, Livorno, Italy. Electronic address: f.cappuzzo@gmail.com.
authors: Federico
authors: F
authors: Cappuzzo
authors: Translational Oncogenomic Unit, National Cancer Institute Regina Elena, Rome, Italy.
authors: Andrea
authors: A
authors: Sacconi
authors: Department of Medical Oncology, Civil Hospital of Livorno, Istituto Toscano Tumori, Livorno, Italy.
authors: Lorenza
authors: L
authors: Landi
authors: S.C. Oncologia Medica, Ospedale Santa Maria della Misericordia, Perugia, Italy.
authors: Vienna
authors: V
authors: Ludovini
authors: Translational Oncogenomic Unit, National Cancer Institute Regina Elena, Rome, Italy.
authors: Francesca
authors: F
authors: Biagioni
authors: Department of Medical Oncology, Civil Hospital of Livorno, Istituto Toscano Tumori, Livorno, Italy.
authors: Armida
authors: A
authors: D'Incecco
authors: Azienda Ospedaliera Universitaria Pisana, U.O. Anatomia ed Istologia Patologica III Universitaria, Pisa, Italy.
authors: Alessandra
authors: A
authors: Capodanno
authors: Department of Medical Oncology, Civil Hospital of Livorno, Istituto Toscano Tumori, Livorno, Italy.
authors: Jessica
authors: J
authors: Salvini
authors: S.C. Oncologia Medica, Ospedale Santa Maria della Misericordia, Perugia, Italy.
authors: Enrichetta
authors: E
authors: Corgna
authors: Department of Medical Oncology, Civil Hospital of Livorno, Istituto Toscano Tumori, Livorno, Italy.
authors: Samanta
authors: S
authors: Cupini
authors: Department of Medical Oncology, Civil Hospital of Livorno, Istituto Toscano Tumori, Livorno, Italy.
authors: Cecilia
authors: C
authors: Barbara
authors: Azienda Ospedaliera Universitaria Pisana, U.O. Anatomia ed Istologia Patologica III Universitaria, Pisa, Italy.
authors: Gabriella
authors: G
authors: Fontanini
authors: S.C. Oncologia Medica, Ospedale Santa Maria della Misericordia, Perugia, Italy.
authors: Lucio
authors: L
authors: Crinò
authors: Translational Oncogenomic Unit, National Cancer Institute Regina Elena, Rome, Italy.
authors: Giovanni
authors: G
authors: Blandino
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D000077544:Panitumumab; D016016:Proportional Hazards Models; D059467:Transcriptome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: Cetuximab; Let-7c; Panitumumab; miR-125b; miR-99a