Novel molecular sub-classification of soft tissue sarcomas

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16660
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kobe University
• Principal Investigator: Komatsu Masato 神戸大学, 医学部附属病院, 助教 (50531753)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 軟部腫瘍

Outline of Final Research Achievements

In soft tissue sarcomas, there is no objective and reproducible molecular markers predicting its malignant potential. To uncover the molecular sub-classification of soft tissue sarcomas according to the expression of cancer-testis antigens (CTAs), which were statistically extracted from publicly available gene-expression database, we performed immunohistochemical analyses of these CTAs using surgically resected sarcoma specimens.
As a result, the higher nuclear expression of DEPDC1A was tend to be associated with shorter progression free survival of patients with leiomyosarcomas and also to be associated with the increased necrotic burden and Ki-67 labeling index, which implying that DEPDC1A is involved in intrinsic malignant manifestation of leiomyosarcomas. As DEPDC1A had been shown to play a critical role for positive regulations in NFKB pathways, DEPDC1A is not only useful for predicting malignant potential, but also would be attractive therapeutic target.

Free Research Field

人体病理学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

悪性腫瘍である肉腫は希少腫瘍の一つで、これまでその悪性度を予測する客観的な分子マーカーの研究・あるいは治療標的の開発が癌腫に比べてが進んでいないことが問題であった。
我々は癌精巣抗原という、精巣と悪性腫瘍でのみ発現がみられる分子に着目したわけだが、1)正常組織では精巣以外の臓器では非常に発現レベルが低く、2)治療標的となった場合に副作用の低減が期待されるという理由がその着眼理由である。
実際DEPDC1Aの高発現が平滑筋肉腫でその悪性度と関連しうることが示され、すでにDEPDC1Aをターゲットとした治療標的の基礎的研究も進んでいることより、平滑筋肉腫の新たな治療展開が期待される。