title: Circulating miR-21 as an independent predictive biomarker for chemoresistance in esophageal squamous cell carcinoma.
abstract: Only a few studies indentified the significance of circulating microRNAs in blood as a predictive biomarker for chemoresistance in esophageal squamous cell carcinoma (ESCC). In this study, we tested whether oncogenic miR-21 promoted chemoresistance in ESCC and served as a biomarker for predicting chemoresistance in plasma of patients with ESCC. All consecutive patients underwent the preoperative chemotherapy regimen (JCOG9907 trial) with cisplatin plus 5-fluorouracil. As a result, pretreatment plasma concentrations of miR-21 were significantly higher in ESCC patients with a low histopathological response than in those with a high histopathological response (P = 0.0416). Multivariate analysis revealed that a high pretreatment plasma concentration of miR-21 was an independent risk factor of chemoresistance (p = 0.0150; Odds Ratio 9.95 (range: 1.56-63.4)). The expression of miR-21 was also significantly higher in pretreatment ESCC tissues with a low histopathological response than in those with a high histopathological response (P = 0.0409). In vitro, although the growth of KYSE 170 ESCC cells transfected with the control mimics was markedly inhibited by the 5-fluorouracil or cisplatin treatment, the inhibitory effects of 5-FU (P < 0.05) or cisplatin (P < 0.05) were significantly reduced in KYSE170 cells that overexpressed miR-21. Taken together, the overexpression of miR-21 contributed to chemoresistance and circulating miR-21 in plasma of patients with ESCC could be a useful biomarker for predicting chemoresistance.
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.
authors: Shuhei
authors: S
authors: Komatsu
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.
authors: Daisuke
authors: D
authors: Ichikawa
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.
authors: Tsutomu
authors: T
authors: Kawaguchi
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.
authors: Mahito
authors: M
authors: Miyamae
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.
authors: Wataru
authors: W
authors: Okajima
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.
authors: Takuma
authors: T
authors: Ohashi
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.
authors: Taisuke
authors: T
authors: Imamura
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.
authors: Jun
authors: J
authors: Kiuchi
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.
authors: Hirotaka
authors: H
authors: Konishi
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.
authors: Atsushi
authors: A
authors: Shiozaki
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.
authors: Hitoshi
authors: H
authors: Fujiwara
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.
authors: Kazuma
authors: K
authors: Okamoto
authors: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.
authors: Eigo
authors: E
authors: Otsuji
keywords: Esophageal cancer; biomarker; chemoresistance; liquid biopsy; microRNA; plasma