MicroRNAs associated with postoperative outcomes in patients with limited stage neuroendocrine carcinoma of the esophagus

Okumura,Tomoyuki; Okumura,Tomoyuki; Fujii,Tsutomu; Fujii,Tsutomu; Terabayashi,Kenji; Terabayashi,Kenji; Kojima,Takashi; Kojima,Takashi; Takeda,Shigeru; Takeda,Shigeru; Kashiwada,Tomomi; Kashiwada,Tomomi; Toriyama,Kazuhiro; Toriyama,Kazuhiro; Hijioka,Susumu; Hijioka,Susumu; Miyazaki,Tatsuya; Miyazaki,Tatsuya; Yamamoto,Miho; Yamamoto,Miho; Tanabe,Shunsuke; Tanabe,Shunsuke; Shirakawa,Yasuhiro; Shirakawa,Yasuhiro; Furukawa,Masayuki; Furukawa,Masayuki; Honma,Yoshitaka; Honma,Yoshitaka; Hoshino,Isamu; Hoshino,Isamu; Nabeya,Yoshihiro; Nabeya,Yoshihiro; Yamaguchi,Hironori; Yamaguchi,Hironori; Uemoto,Shinji; Uemoto,Shinji; Shimada,Yutaka; Shimada,Yutaka; Matsubara,Hisahiro; Matsubara,Hisahiro; Ozawa,Soji; Ozawa,Soji; Makuuchi,Hiroyasu; Makuuchi,Hiroyasu; Imamura,Masayuki; Imamura,Masayuki

doi:10.3892/ol.2023.13862

MicroRNAs associated with postoperative outcomes in patients with limited stage neuroendocrine carcinoma of the esophagus

Authors:
- Tomoyuki Okumura
- Tsutomu Fujii
- Kenji Terabayashi
- Takashi Kojima
- Shigeru Takeda
- Tomomi Kashiwada
- Kazuhiro Toriyama
- Susumu Hijioka
- Tatsuya Miyazaki
- Miho Yamamoto
- Shunsuke Tanabe
- Yasuhiro Shirakawa
- Masayuki Furukawa
- Yoshitaka Honma
- Isamu Hoshino
- Yoshihiro Nabeya
- Hironori Yamaguchi
- Shinji Uemoto
- Yutaka Shimada
- Hisahiro Matsubara
- Soji Ozawa
- Hiroyasu Makuuchi
- Masayuki Imamura
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Affiliations: Department of Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama 930‑0194, Japan, Department of Mechanical and Intellectual Systems Engineering, Faculty of Engineering, University of Toyama, Toyama 930‑8555, Japan, Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba 277‑8577, Japan, Department of Gastroenterological, Breast and Endocrine Surgery, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi 755‑8505, Japan, Department of Medical Oncology, Division Hematology, Respiratory Medical and Oncology, Saga University, Saga 849‑8501, Japan, Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Aichi 464‑8681, Japan, Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan, Department of Gastroenterological Surgery, Tokai University School of Medicine, Isehara, Kanagawa 259‑1193, Japan, Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700‑8558, Japan, Department of Hepato‑Biliary‑Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka 811‑1395, Japan, Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo 104‑0045, Japan, Division of Gastroenterological Surgery, Chiba Cancer Center, Chiba 260‑8717, Japan, Department of Clinical Oncology, Jichi Medical University, Shimotsuke, Tochigi 329‑0498, Japan, President's Office, Shiga University of Medical Science, Otsu, Shiga 520‑2192, Japan, Department of Nanobio Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606‑8501, Japan, Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260‑8670, Japan, Neuroendocrine Tumor Center, Kansai Electric Power Hospital, Osaka 553‑0003, Japan
Published online on: May 12, 2023 https://doi.org/10.3892/ol.2023.13862
Article Number: 276
Copyright: © Okumura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Esophageal neuroendocrine carcinoma (E‑NEC) is an aggressive disease with a poor prognosis. The present study aimed to assess the role of surgery in the treatment of patients with resectable E‑NEC, and identify a microRNA (miRNA/miR) signature in association with positive postoperative outcomes. Between February 2017 and August 2019, 36 patients with E‑NEC who underwent curative surgery at the Japan Neuroendocrine Tumor Society partner hospitals were enrolled in the study. A total of 16 (44.4%) patients achieved disease‑free survival (non‑relapse group), whereas 20 (55.6%) patients developed tumor relapse (relapse group) during the median follow‑up time of 36.5 months (range, 1‑242) after surgery with a 5‑year overall survival rate of 100 and 10.8%, respectively (P<0.01). No clinicopathological parameters, such as histological type or TNM staging, were associated with tumor relapse. Microarray analysis of 2,630 miRNAs in 11 patients with sufficient quality RNA revealed 12 miRNAs (miR‑1260a, ‑1260b, ‑1246, ‑4284, ‑612, ‑1249‑3p, ‑296‑5p, ‑575, ‑6805‑3p, ‑12136, ‑6822‑5p and ‑4454) that were differentially expressed between the relapse (n=6) and non‑relapse (n=5) groups. Furthermore, the top three miRNAs (miR‑1246, ‑1260a and ‑1260b) were associated with overall survival (P<0.01). These results demonstrated that surgery‑based multidisciplinary treatment is effective in a distinct subpopulation of limited stage E‑NEC. A specific miRNA gene set is suggested to be associated with treatment outcome.

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