Role of Neuroendocrine Factors in chemo-sensitivity for large cell neuroendocrine Carcinoma

• Project/Area Number: 18K08782
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Kobe University
• Principal Investigator: TANAKA YUGO 神戸大学, 医学部附属病院, 講師 (20403256)
• Co-Investigator(Kenkyū-buntansha): 眞庭 謙昌 神戸大学, 医学研究科, 教授 (50362778)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 肺癌 / 高悪性度神経内分泌癌 / 小細胞肺癌 / 外科治療 / 大細胞神経内分泌肺癌 / 術後補助化学療法

Outline of Final Research Achievements

We examined 35 cases of large cell neuroendocrine lung carcinoma (LCNEC) under 3 cm or less who underwent anatomical lung resection at our institution. We concluded that "the higher the neuroendocrine factor, the higher the likelihood of LCNEC being closer to small cell lung cancer."
Insulinoma-associated protein 1 (INSM1), which has known as new neuroendocrine factor, was examined for its relevance to prognosis using 75 lung surgically resected specimens at our institution. We concluded that the overall survival and recurrence-free survival were significantly shorter in INSM1 positive patients than INSM1 negative patients. In addition, multivariate analysis confirmed that INSM1 was a significant factor with a poor prognosis.

Academic Significance and Societal Importance of the Research Achievements

高悪性度神経内分泌肺癌は非常に予後不良な組織型である。小細胞癌、大細胞神経内分泌肺癌が含まれているが、治療後の予後に関しては神経内分泌肺癌の有無により差があることが報告されている。今回、Insulinoma-associated protein 1(INSM1)について予後との関連性を検討したところ、これまでの因子以上にその有無により予後に大きな差が認められた。今後、同因子をターゲットにした治療方法を検討していくことが個別化医療につながると確信している。

Research Products

• [Journal Article] Insulinoma‐associated protein 1 is a prognostic biomarker in pulmonary high‐grade neuroendocrine carcinoma (2020)
  • Author(s): Minami Kazuhiro、Jimbo Naoe、Tanaka Yugo、Ogawa Hiroyuki、Hokka Daisuke、Nishio Wataru、Yoshimura Masahiro、Itoh Tomoo、Maniwa Yoshimasa
  • Journal Title: Journal of Surgical Oncology Volume: 1 Issue: 2 Pages: 1-11
  • DOI: 10.1002/jso.25960
  • Peer Reviewed / Open Access
• [Journal Article] Neuroendocrine marker staining pattern categorization of small‐sized pulmonary large cell neuroendocrine carcinoma (2019)
  • Author(s): Minami Kazuhiro、Tanaka Yugo、Ogawa Hiroyuki、Jimbo Naoe、Nishio Wataru、Yoshimura Masahiro、Itoh Tomoo、Maniwa Yoshimasa
  • Journal Title: Thoracic Cancer Volume: 10 Issue: 11 Pages: 2152-2160
  • DOI: 10.1111/1759-7714.13202
  • NAID: 120006764479
  • Peer Reviewed / Open Access
• [Presentation] 肺高悪性度神経内分泌癌の予後バイオマーカーとしての インスリノーマ関連タンパク質1の検討 (2020)
  • Author(s): 南 和宏, 田中 雄悟, 岡本 武士, 清水 奈保子, 土井 健史, 法華 大助, 眞庭 謙昌
  • Organizer: 第73回日本胸部外科学会定期学術集会
• [Presentation] Neuroendocrine marker staining pattern categorization of small-sized pulmonary large cell neuroendocrine carcinoma (2019)
  • Author(s): Kazuhiro Minami, Yugo Tanaka, Takeshi Okamoto, Nahoko Shimizu, Takefumi Doi, Hiroyuki Ogawa, Daisuke Hokka, Naoe Jimbo, Wataru Nishio, Masahiro Yoshimura, Tomoo Itoh, Yoshimasa Maniwa
  • Organizer: World Conference on Lung Cancer
  • Int'l Joint Research