Oncotarget

Research Papers:

Plasma microRNA profiles: identification of miR-23a as a novel biomarker for chemoresistance in esophageal squamous cell carcinoma

Shuhei Komatsu _, Daisuke Ichikawa, Tsutomu Kawaguchi, Hiroki Takeshita, Mahito Miyamae, Takuma Ohashi, Wataru Okajima, Taisuke Imamura, Jun Kiuchi, Tomohiro Arita, Hirotaka Konishi, Atsushi Shiozaki, Hitoshi Fujiwara, Kazuma Okamoto and Eigo Otsuji

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Oncotarget. 2016; 7:62034-62048. https://doi.org/10.18632/oncotarget.11500

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Abstract

Shuhei Komatsu1,*, Daisuke Ichikawa1, Tsutomu Kawaguchi1,*, Hiroki Takeshita1, Mahito Miyamae1, Takuma Ohashi1, Wataru Okajima1, Taisuke Imamura1, Jun Kiuchi1, Tomohiro Arita1, Hirotaka Konishi1, Atsushi Shiozaki1, Hitoshi Fujiwara1, Kazuma Okamoto1, Eigo Otsuji1

1Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

*These authors contributed equally to this work

Correspondence to:

Shuhei Komatsu, email: [email protected]

Keywords: plasma, microRNA, biomarker, prognosis, chemoresistance

Received: March 27, 2016     Accepted: August 10, 2016     Published: August 22, 2016

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).

MATERIALS AND 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.


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