Identification of Diagnostic Markers for Malignant Mesothelioma Using Innovative Mass Spectrometry

2020 Fiscal Year Final Research Report

• Project/Area Number: 17H04059
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: The Tazuke Kofukai (2020); Kyoto University (2017-2019)
• Principal Investigator: Tsuruyama Tatsuaki 公益財団法人田附興風会, 医学研究所 第1研究部, 研究員 (00303842)
• Co-Investigator(Kenkyū-buntansha): 吉澤 明彦 京都大学, 医学研究科, 准教授 (80378645) ; 平塚 拓也 京都大学, 医学研究科, 特定講師 (90641639)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 悪性中皮腫 / 質量分析 / タンパク質 / バイオマーカー

Outline of Final Research Achievements

We extracted proteins from 24 tissue sections collected from epithelioid malignant pleural mesothelioma (EMPM) and normal mesothelial cells (NM). The abundance of individual proteins in each tissue sample was assessed using liquid chromatography-mass spectrometry (LC/MS). RhoA, a highly susceptible mutation locus, were significantly higher in EMPM than in NM tissues. Besides, endoplasmic reticulum related proteins, including vigilin and redox-oxidation control proteins including PRDX4, and ubiquitin E3 ligase, were significantly higher in EMPM than in NM tissues. Immunohistochemistry (IHC) of 93 MM (epithelioid, 71 cases; sarcomatoid, 13 cases; biphasic, 9 cases), 64 lung adenocarcinoma (LAC), 60 lung squamous cell carcinoma (LSC), and 14 NM tissues was performed. RhoA and vigilin revealed positivity of EMPM, and PRDX4 and ubiquitin E3 ligase were positive in most MMs and the majority of LAC and LSC. This profiling suggests that the stress-induced reaction relates to MM pathogenesis.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

悪性中皮腫の腫瘍発生に関する病因はいまだ明確でなく、その早期診断マーカーや治療の早期開発が強く望まれている。今回の研究で、活性酸素、プロテアソーム、小胞体ストレスに関するタンパク質の発現の増加が悪性中皮腫で顕著であり、その腫瘍発生のメカニズムの概観が可能になった。また治療法開発についても酸化ストレス、プロテアソーム、小胞体ストレスの関連分子を標的としたあらたな方法の開発の有効性を示唆している。