title: Association of MicroRNA-31-5p with Clinical Efficacy of Anti-EGFR Therapy in Patients with Metastatic Colorectal Cancer.
abstract: BACKGROUND
  Gene mutations in the pathway downstream of epidermal growth factor receptor (EGFR) are considered to induce resistance to anti-EGFR therapy in colorectal cancer (CRC). We recently reported that microRNA-31 (miR-31)-5p may regulate BRAF activation and play a role in the signaling pathway downstream of EGFR in CRC. Therefore, we hypothesized that miR-31-5p can be a useful biomarker for anti-EGFR therapy in CRC.
  
  
  METHODS
  We evaluated miR-31-5p expression and gene mutations [KRAS (codon 61 or 146), NRAS (codon 12, 13, or 61), and BRAF (V600E)] in the EGFR downstream pathway in 102 CRC patients harboring KRAS (codon 12 or 13) wild-type who were treated with anti-EGFR therapeutics. Progression-free survival (PFS) and overall survival (OS) were evaluated.
  
  
  RESULTS
  KRAS (codon 61 or 146), NRAS, and BRAF mutations were detected in 6.9, 6.9, and 5.9 % patients, respectively. Compared with CRCs with at least one mutation (n = 20), significantly better PFS (P = 0.0003) but insignificantly better OS were observed in CRCs harboring all wild-type genes (KRAS, NRAS, and BRAF). High miR-31-5p expression was identified in 11 % (n = 11) patients and was significantly associated with shorter PFS (P = 0.003). In CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS (P = 0.027).
  
  
  CONCLUSIONS
  High miR-31-5p expression was associated with shorter PFS in patients with CRC treated with anti-EGFR therapeutics. Moreover, in CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS, suggesting that it may be a useful and additional prognostic biomarker for anti-EGFR therapy.
authors.affiliation: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Igarashi
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Kurihara
authors.forename: Kei
authors.initials: K
authors.lastname: Mitsuhashi
authors.forename: Miki
authors.initials: M
authors.lastname: Ito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okuda
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kanno
authors.forename: Takafumi
authors.initials: T
authors.lastname: Naito
authors.forename: Shinji
authors.initials: S
authors.lastname: Yoshii
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Takaya
authors.initials: T
authors.lastname: Kusumi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Sukawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Adachi
authors.forename: Kenji
authors.initials: K
authors.lastname: Okita
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Yu
authors.initials: Y
authors.lastname: Imamura
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Baba
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nosho
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D000068818:Cetuximab / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000077544:Panitumumab; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D066066:Response Evaluation Criteria in Solid Tumors; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; C534612:MIRN31 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D000077544:Panitumumab; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab