title: Plasma microRNA profiles: identification of miR-23a as a novel biomarker for chemoresistance in esophageal squamous cell carcinoma.
abstract: BACKGROUND
  This study aims to explore novel microRNAs in plasma for predicting chemoresistance in preoperative chemotherapy of patients with esophageal squamous cell carcinoma (ESCC) using a microRNA array-based approach.
  
  
  RESULTS
  (1) Four candidate microRNAs (miR-223, 103a, 23b and 23a), which were highly expressed in the pretreatment plasma of patients with a low histopathologic response, were selected. (2) In a large-scale validation analysis by quantitative RT-PCR, plasma levels of miR-223, miR-23b and miR-23a were significantly higher in patients with a low histopathologic response than in those with a high histopathologic response (p = 0.0345, p = 0.0125 and p = 0.0114). (3) Of all candidate microRNAs, miR-23a expression of pretreatment ESCC tumor tissues was significantly higher in ESCC patients with a low histopathologic response than in those with a high histopathologic response (p = 0.0278). (4) After overexpressing each candidate in ESCC cells, miR-23a induced significant chemoresistance to both 5-fluorouracil and cisplatin, and miR-223 to cisplatin in vitro. (5) A high level of plasma miR-23a, which tended to correlate with lymphatic invasion (p = 0.0808) and deep depth of invasion (p = 0.0658), was an independent risk factor for chemoresistance in ESCC (p = 0.0222; odds ratio: 12.4; range 1.46-105).
  
  
  METHODS
  We used the Toray® 3D-Gene microRNA array-based approach to compare plasma microRNA levels between patients with a high or a low histopathologic response to chemotherapy. All patients underwent a preoperative chemotherapy regimen with cisplatin plus 5-fluorouracil.
  
  
  CONCLUSIONS
  Plasma miR-23a might be a useful biomarker for predicting chemoresistance in ESCC patients.
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Shuhei
authors: S
authors: Komatsu
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Daisuke
authors: D
authors: Ichikawa
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Tsutomu
authors: T
authors: Kawaguchi
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Hiroki
authors: H
authors: Takeshita
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Mahito
authors: M
authors: Miyamae
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Takuma
authors: T
authors: Ohashi
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Wataru
authors: W
authors: Okajima
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Taisuke
authors: T
authors: Imamura
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Jun
authors: J
authors: Kiuchi
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Tomohiro
authors: T
authors: Arita
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Hirotaka
authors: H
authors: Konishi
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Atsushi
authors: A
authors: Shiozaki
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Hitoshi
authors: H
authors: Fujiwara
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Kazuma
authors: K
authors: Okamoto
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Eigo
authors: E
authors: Otsuji
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016017:Odds Ratio; D011379:Prognosis; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; C544749:MIRN103 microRNA, human; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D002945:Cisplatin; D005472:Fluorouracil
keywords: biomarker; chemoresistance; microRNA; plasma; prognosis