Identification of novel therapeutic targets for ovarian cancer by surfaceome analysis

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15386
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Kobayashi Makoto 福島県立医科大学, 医学部, 助教 (60761947)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 卵巣癌 / 予後マーカー / 細胞表面タンパク質 / プロテオミクス

Outline of Final Research Achievements

In-depth proteomics analysis revealed 9,000 proteins expressed on the surface of serous ovarian cancer cells. First, using bioinformatics analysis, we discovered Spondin-1 (SPON1) as a protein with a "cell surface signature" that was particularly expressed in ovarian cancer compared to other cancer types. Second, we generated a monoclonal antibody against SPON1 and investigated the correlation between SPON1 expression and clinicopathological factors using immunohistochemistry. Our findings suggested that high SPON1 expression was an independent prognostic factor for ovarian cancer recurrence-free survival. Furthermore, we found SPON1 secretion in both ovarian cancer cell culture media and ovarian cancer patient-derived ascites fluid. With these findings, SPON1 has been identified not only as a prognostic marker but also as a serum diagnostic marker for ovarian cancer.

Free Research Field

人体病理

Academic Significance and Societal Importance of the Research Achievements

細胞表面タンパク質は、がんの診断・治療標的候補として有望な分子群が濃縮されていると考えられる。しかしながら、実際に卵巣癌細胞の表面に発現するタンパク質を詳細に解析した報告は少ない。本研究で着目したSPON1は、自身が組織診断・予後マーカー、血清診断マーカー、治療標的としての可能性を持つ。従って本研究で確立した細胞表面タンパク質の網羅的同定法は、卵巣癌の新規バイオマーカーの獲得法として有用である。また我々が絞り込んだ他の分子群についても同様に卵巣癌の新規バイオマーカーや治療標的としての有用性が示唆され、卵巣癌の予後延長に寄与できることが期待される。