Identification of a miRNA panel for predicting recurrence after surgery in pancreatic cancer by comprehensive analysis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16385
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Nara Medical University
• Principal Investigator: Nishiwada Satoshi 奈良県立医科大学, 医学部, 研究員 (80745795)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 膵癌 / microRNA / 術後再発予測パネル

Outline of Final Research Achievements

We performed biomarker discovery to identify an Axon guidance-related miRNA panel (AGMP) for risk-stratification of perivascular plexus recurrence (PPR) after surgery in PDAC. The pathway-miRNA interaction analysis using the miRPathDB 2.0 identified 13 miRNAs related to the axon guidance pathway. Subsequently, the predictive performance of the 13-miRNA risk-prediction model, AGMP was trained and validated in three independent surgically resected sample cohorts [Upfront surgery (US) cohort: n = 162, NACRT cohort: n = 217, Arterial invasion cohort: n = 62], which robustly distinguished PPR after surgery in the US (AUC: 0.95), NACRT (AUC: 0.94), and Arterial invasion cohort (AUC: 0.91). Furthermore, we additionally validated the performance of AGMP in a pretreatment blood cohort (n = 53), which again confirmed the robustness of risk-stratification for PPR (AUC: 0.86). Conclusions: We developed a novel biomarker, AGMP, that demonstrated remarkable predictive performance for PPR in PDAC.

Free Research Field

膵癌

Academic Significance and Societal Importance of the Research Achievements

膵癌は最も悪性度の高い癌であり，世界的に増加すると予想されている．完全なる局所制御が根治に必須であるが，膵癌は大血管周囲神経叢に容易に浸潤を来し，根治術後であっても高率に局所再発を来す．近年，癌と神経新生，軸索誘導 (Axon Guidance, AG) との関連性が着目されており，この関連分子が神経周囲浸潤や転移を促進するとの報告がある．今回我々は統合解析を基に，膵癌術後神経叢局所再発予測AG関連miRNAパネル (AGMP) を開発した．膵癌手術における局所制御は根治に向けた大前提であり，その術前予測を可能とするAGMPは手術適応の厳格化および治療方針決定においてブレイクスルーとなり得る．