Gene expression profile and therapeutic targets in high-grade spindle cell sarcomas focusing on the gene regulation system.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16753
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Juntendo University
• Principal Investigator: Akaike Keisuke 順天堂大学, 医学部, 非常勤助教 (60801719)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 肉腫 / 筋原性 / 平滑筋肉腫 / myostatin

Outline of Final Research Achievements

Pleomorphic leiomyosarcoma (PLMS) is a high-grade sarcoma composed of typical LMS with a dedifferentiated high-grade area. The mechanisms of myogenic differentiation in high-grade sarcomas are unknown. We employed Cap Analysis of Gene Expression (CAGE) analysis to elucidate the possible gene expression networks that could discriminate PLMS from other high-grade sarcomas. MSTN promoters, encoding myostatin were more activated in high-grade sarcomas that did not show morphological and immunohistochemical smooth muscle differentiation compared to PLMS. Immunohistochemistry showed reduction or loss of myostatin expression encoded by MSTN in PLMS but not in other high-grade sarcomas. Furthermore, immunohistochemical double staining revealed that the expression patterns of myostatin and myogenic markers were almost mutually exclusive in these tumors. These findings suggest that myostatin acts as a regulator of myogenic differentiation in high-grade sarcomas.

Free Research Field

骨軟部腫瘍病理

Academic Significance and Societal Importance of the Research Achievements

希少がんであること、かつ専門とする病理医も少ない分野における軟部肉腫の病理診断において、従来の免疫染色マーカーだけでなく、myostatinの免疫染色も行うことによって、専門性の高い軟部肉腫の病理診断に役立つ可能性が示された。また、遺伝子発現解析の結果からは、多型型平滑筋肉腫は他の高悪性度肉腫とは異なる性格を有する可能性が示唆されたことから、これらの高悪性度肉腫をしっかり病理組織学的に分類していく必要性があること、さらには腫瘍特異的な治療法の確立が望まれることが示唆された。