MicroRNA profiles to predict postoperative prognosis in patients with esophageal neuroendocrine carcinoma

Research Project

Project/Area Number	18K08642
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	University of Toyama
Principal Investigator	Okumura Tomoyuki 富山大学, 学術研究部医学系, 講師 (10533523)
Co-Investigator(Kenkyū-buntansha)	嶋田裕京都大学, 薬学研究科, 客員教授 (30216072) 藤井努富山大学, 学術研究部医学系, 教授 (60566967)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	食道癌 / 神経内分泌腫瘍 / マイクロRNA / 食道神経内分泌癌 / 遺伝子発現 / 食道神経内分泌細胞癌 / 食道 / 神経内分泌癌 / 癌幹細胞
Outline of Final Research Achievements	RNA was extracted from 36 surgical specimens of esophageal neuroendocrine carcinoma (NEC) patients who received surgery at 12 hospitals which were member of the Japan Neuro Endocrine Tumor Society (JNETS). After quality check of the RNA, microRNA expression was detected using micro array in 18 cases. Our microarray analysis identified 75 miRNAs that were differentially expressed between paired SCCE tumors and their corresponding normal samples. Forty-eight miRNAs were differentially expressed between the two groups and associated with the malignant features. Hierarchical clustering of 32 miRNA expression levels revealed two distinct sub-groups that were identical to the patients with long-term postoperative survival and to those with rapid tumor relapse, respectively. These results suggested the existence of a specific miRNA signature that could be used to predict postoperative outcomes.
Academic Significance and Societal Importance of the Research Achievements	食道原発神経内分泌癌(NEC)は食道癌の1%と非常に希であり、エビデンスに基づく標準治療の確立には至っていない。通常の食道癌と比べて悪性度が高いことが知られており、切除可能症例においても術後早期に再発し救命できない症例が少なからず経験される。本研究の成果によって悪性度と相関する分子生物学的サブクラスが同定され、食道NECにおける遺伝子スクリーニングに基づく切除適応症例選択が実現し個別化医療が確立されるものと期待される。さらに本研究によって同定された遺伝子セットの機能解析によって新たな治療法の開発につながる可能性が期待される。