Identification and clinical application of the colon cancer-specific protein markers

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09123
• 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: Ehime University
• Principal Investigator: Watanabe Yuji 愛媛大学, 医学系研究科, 教授 (20210958)
• Co-Investigator(Kenkyū-buntansha): 東山 繁樹 愛媛大学, プロテオサイエンスセンター, 教授 (60202272)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 大腸癌 / KLHL5 / CUL3 / ユビキチンリガーゼ / バイオマーカー

Outline of Final Research Achievements

KLHL5, a substrate receptor of CUL3-based ubiquitin E3 ligase, shows positive correlation to the proliferation and invasiveness of colorectal cancer. We performed the screening of KLHL5-binding proteins by an AlphaScreen assay based on human 2000 protein array, and identified 98 proteins as KLHL5-subsrate candidates. We further identified proteotypic peptides of 98 proteins by Mass analysis, constructed KLHL5-substrate protein #2 QconCAT, and then established a selective reaction monitoring system (KLHL5-substrate SRM) for simultaneous quantification of KLHL5-substrates. KLHL5-substrate SRM analysis revealed 3 proteins as KLHL5 target substrates in colorectal cancer cell lines, HCT116 and SW480 cells. We are currently identifying and characterizing KLHL5 target substrate-related factors as diagnostic markers of colorectal cancer.

Free Research Field

医学

Academic Significance and Societal Importance of the Research Achievements

これまでに大腸がん領域では、化学療法に感受性及び毒性の指標となるバイオマーカーの開発が続けられているが、臨床応用可能な大腸がん特異的バイオマーカーは未だ見出されていない。我々のこれまでの研究並びに本研究において見出した大腸がん悪性化相関性因子KLHL5とその標的基質タンパク質関連因子が、新たな大腸がんバイオマーカーとなり得る可能性を示唆できた。大腸がん診断の新規マーカー分子の確立は、予後を予測し、切除可能な状態で発見することや、早期に化学療法を導入することに役立ち、社会的意義は極めて大きい。