Development of Novel Therapeutic Methods Based on Metabolomic and Genetic Analysis for the Control of Ovarian Cancer Cachexia

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09532
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Yamagata University
• Principal Investigator: Nagase Satoru 山形大学, 医学部, 教授 (00292326)
• Co-Investigator(Kenkyū-buntansha): 清野 学 山形大学, 医学部, 講師 (40594320) ; 太田 剛 山形大学, 医学部, 准教授 (50375341)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 卵巣癌 / 腹水 / メタボローム解析 / アミノ酸代謝 / ポリアミン経路

Outline of Final Research Achievements

The present study demonstrated that amino acid metabolism, urea circuit (polyamine pathway), energy metabolism such as sugar and TCA metabolism, one carbon metabolism such as choline metabolism, and nucleic acid metabolism pathways were enhanced in ascites obtained from patients with ovarian cancer compared to ascites from patients with benign disease. These metabolic pathways were also enhanced in tumor tissues. In addition, the production of many amino acids was significantly elevated in tumor tissues compared to normal tissues, but only kynurenine was significantly elevated in ascites fluid of ovarian cancer compared to ascites of benign disease. It is suggested that the amino acid profile is altered in acquiring distant metastatic potential and that the increased production of kynurenine, especially in ascites, may be important in the formation of metastasis to other organs.

Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

卵巣癌は初期に自覚症状が乏しく、発見時には腹膜播種や腹水貯留を来した、進行した状態で見つかることが多い。腹水量は腫瘍の摘出達成の予測や治療戦略に影響を与え、再発の指標にもなるため、重要な指標とされるが、腹膜播種や腹水貯留が多い症例の最適な治療法は確立されていない。本研究では、卵巣癌腹水中では遠隔転移能を獲得する上でアミノ酸プロファイルが変化し、特にキヌレニン産生の上昇が他臓器への転移病巣形成に重要である可能性が示唆された。キヌレイン産生を阻害することで腹水産生と播種を抑制する新たな治療法となり得る可能性を示した点で学術的、社会的意義がある。