Development of novel diagnostic markers for pancreatic cancer focused on the tumor microenvironment associated with hypoxia and nutrient depletion.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09093
• 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: Kanagawa Cancer Center Research Institute
• Principal Investigator: miyagi yohei 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), 臨床研究所, 所長 (00254194)
• Co-Investigator(Kenkyū-buntansha): 廣島 幸彦 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), 臨床研究所, 医長 (60718021) ; 森永 聡一郎 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), その他部局等, その他 (80244432)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 低酸素 / 低栄養 / 膵癌 / 腫瘍マーカー / 早期診断

Outline of Final Research Achievements

In this study, we attempted to develop early diagnostic markers for pancreatic cancer, which is highly refractory and difficult to diagnose due to the lack of appropriate tumor markers and imaging diagnostics. First, we identified several genes whose expression is specifically induced under hypoxic and nutrient-starved conditions in cultured human pancreatic cancer cells, along with the proteins encoded by these genes. Among these, we focused on a single molecule that demonstrated high novelty and the potential for its protein or related substances to appear in the bloodstream. We established a detection system for this molecule. Furthermore, we confirmed through mass spectrometry that the small molecules produced by this protein with enzymatic activity appeared in the cells and the cell culture supernatant. In silico analysis also confirmed that these substances are present in trace amounts in the blood, and we constructed a measurement system for them.

Free Research Field

腫瘍病理学、分子腫瘍学、ゲノム病理学

Academic Significance and Societal Importance of the Research Achievements

がんの新たな早期発見手法の活用による２次予防の推進は、第５次がん研究１０か年戦略の具体的研究事項にも挙げられている。単に細胞や組織の増殖速度に着目するだけでは、非がん組織とがんを区別し早期診断を実現する腫瘍マーカーの開発ができないことは、消化管粘膜上皮、骨髄、子宮内膜などの存在から想像に難くない。本研究では、難治性の膵がんの診断マーカー候補を見出すと同時に、培養ヒトがん細胞を低酸素・栄養飢餓状態にして発現が特異的に誘導される遺伝子群から早期診断マーカーを探索する手法の実例を提示することができた。