Novel biomarkers distinguishing pancreatic head Cancer from distal cholangiocarcinoma based on proteomic analysis

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16527
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Tohoku University
• Principal Investigator: Maeda Shimpei 東北大学, 医学系研究科, 大学院非常勤講師 (90455824)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 膵頭部癌 / タンパク質バイオマーカー / 遠位胆管癌 / 免疫組織化学

Outline of Final Research Achievements

Ten PHC and 8 DCC specimens were analyzed by LC-MS/MS. Selected proteins were evaluated, using immunohistochemical analysis, to determine whether they would be appropriate biomarkers. Finally, we generated biomarker panels to improve diagnostic accuracy. 1820 proteins were detected using LC-MS/MS. Fifteen differentially expressed proteins were selected as candidates based on semi-quantitative comparison. We first performed immunohistochemical staining on samples from the small cohort group using 15 candidates. KRT17, ANXA10, TMEM109, PTMS, and ATP1B1 showed favorable performances and were tested in the next large cohort group. KRT17 performed best for the diagnosis of PHC as a single marker; additionally, PTMS exhibited good performance for the diagnosis of DCCs. Moreover, we indicated the KRT17+/ANXA10+/PTMS- staining pattern as a biomarker panel for the correct diagnosis of PHC.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

タンパク質発現プロファイルを解析し、免疫組織化学的検証を経て、膵頭部癌と遠位胆管癌の診断を可能とする5種類のタンパク質を同定した。膵頭部癌の診断に有用なバイオマーカーは、単独ではKRT17であり、バイオマーカーパネルとしてはKRT17陽性/ANXA10陽性/TMEM109陽性を示す表現型であった。一方遠位胆管癌の診断に最も有用なバイオマーカーはPTMSであり、バイオマーカーパネルはKRT17陰性/ANXA10陰性/ PTMS陽性を示す表現型であった。これらのバイオマーカーは膵頭部癌と遠位胆管癌の新規鑑別診断マーカーとして有望であり、現状では鑑別困難な症例に臨床応用できる可能性がある。