Rubicon can predict prognosis in patients of pancreatic ductal adenocarcinoma after neoadjuvant chemoradiotherapy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09121
• 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: National Hospital Organization Osaka National Hospital Institute for Clinical Reserch (2021); Osaka University (2019-2020)
• Principal Investigator: Gotoh Kunihito 独立行政法人国立病院機構大阪医療センター(臨床研究センター), その他部局等, 研究員 (10362716)
• Co-Investigator(Kenkyū-buntansha): 小林 省吾 大阪大学, 医学系研究科, 准教授 (30452436) ; 江口 英利 大阪大学, 医学系研究科, 教授 (90542118)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Rubicon / 膵癌 / autophagy / 化学療法 / Gemcitabine

Outline of Final Research Achievements

To evaluate the clinical significance of Rubicon, immunohistochemistry was performed, and Rubicon expression was analyzed in specimens resected from pancreatic ductal adenocarcinoma (PDAC) patients after neoadjuvant chemoradiotherapy. We established Gemcitabine-resistant (GR) PDAC cell line, estimated Rubicon expression and Autophagy Flux, and evaluated gemcitabine (GEM) sensitivity, invasion ability, and cell viability, using small interfering RNA (siRNA) targeting Rubicon.
Rubicon expression in resected PDAC after chemoradiotherapy samples revealed significantly worse overall survival and recurrence-free survival in the Rubicon-high expression than in the Rubicon-low group. In vitro, GR PDAC cell lines had higher expression and lower autophagy flux than parent PDAC cell line. Transduction with siRNA downregulated Rubicon, which did not affect on GEM sensitivity but did reduce invasion ability and cell viability in GR PDAC cell line.

Free Research Field

膵癌

Academic Significance and Societal Importance of the Research Achievements

Rubiconの高発現は、化学放射線療法後の膵癌患者において予後不良な因子であり、細胞実験でRubiconを抑制することでゲムシタビン抵抗性膵癌細胞株の浸潤能と細胞生存率を改善することが示された。以上より、化学放射線療法後の膵癌において、Rubicon高発現が予後不良因子であり、またRubiconをターゲットとした治療が、癌治療後の膵癌において有効な治療法の選択肢の一つになりうる可能性が示唆された。