analysis on genetic abnormality related to aggressive behavior of uterine leiomyosarcoma

• Project/Area Number: 16K11124
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Hokkaido University
• Principal Investigator: Watari Hidemichi 北海道大学, 医学研究院, 教授 (10344508)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 子宮平滑筋肉腫 / leiomyosarcoma / ncounter / microarray / gene expression profile / 子宮肉腫 / 遺伝子異常 / アレイ解析

Outline of Final Research Achievements

Formalin-fixed paraffin embedded (FFPE) tissue specimens of uterine leiomyosarcoma were used for gene expression profile analysis (SurePrint G3Human GE8x60K v3, agilent), and digital count gene expression analysis (ncounter) compared with normal uterine muscle tissue specimens. Using PanCancerImmune Profiling for Human panel, difference of immune environment was analyzed between normal and leiomyosarcoma tissues. We found that the number of immune cells decreased in leiomyosarcoma compared with normal tissue. Additionally, we analyzed the relationship between tumor immunity and prognosis among six leiomyosarcoma patients with stage I disease who underwent hysterectomy+bilateral salpingooophorectomy and adjuvant chemotherapy. T cell immunity was activated in the patients who survived after 12 months after initial treatment compared with those who died within 12 months.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果、腫瘍浸潤リンパ球は重要な予後因子であり、個々の腫瘍の分子生物学的な特徴と増殖過程で形成される微小環境との関連を検討し、その最適化を行うことが子宮平滑筋肉腫患者の予後を改善する方法になるものと推察された。今後、子宮平滑筋肉腫に対する有効な治療開発を行うにあたり、抗がん薬や放射線療法とＰＤ１－ＰＤＬ１経路などの免疫チェックポイント阻害薬の併用や腫瘍浸潤Ｔリンパ球輸注療法との併用の有効性についての検討を行うことで、きわめて予後不良な子宮平滑筋肉腫の治療成績向上に資する可能性が示唆された。

Research Products

• [Journal Article] Tumor-Intrinsic PD-L1 Signaling in Cancer Initiation, Development and Treatment: Beyond Immune Evasion (2018)
  • Author(s): Dong Peixin、Xiong Ying、Yue Junming、Hanley Sharon J. B.、Watari Hidemichi
  • Journal Title: Frontiers in Oncology Volume: 8 Pages: 386-396
  • DOI: 10.3389/fonc.2018.00386
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] B7H3 As a Promoter of Metastasis and Promising Therapeutic Target (2018)
  • Author(s): Dong Peixin、Xiong Ying、Yue Junming、Hanley Sharon J. B.、Watari Hidemichi
  • Journal Title: Frontiers in Oncology Volume: 8 Pages: 264-268
  • DOI: 10.3389/fonc.2018.00264
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Long Non-coding RNA NEAT1: A Novel Target for Diagnosis and Therapy in Human Tumors (2018)
  • Author(s): Dong Peixin、Xiong Ying、Yue Junming、Hanley Sharon J. B.、Kobayashi Noriko、Todo Yukiharu、Watari Hidemichi
  • Journal Title: Frontiers in Genetics Volume: 9 Pages: 471-451
  • DOI: 10.3389/fgene.2018.00471
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comparison of human papillomavirus genotyping and cytology triage, COMPACT Study: Design, methods and baseline results in 14 642 women (2018)
  • Author(s): Aoyama-Kikawa Satomi、Fujita Hiromasa、Hanley Sharon J.B.、Kasamo Mitsunori、Kikuchi Kokichi、Torigoe Toshihiko、Matsuno Yoshihiro、Tamakoshi Akiko、Sasaki Takayuki、Matsuura Motoki、Kato Yasuhito、Dong Peixin、Watari Hidemichi、Saito Tsuyoshi、Sengoku Kazuo、Sakuragi Noriaki
  • Journal Title: Cancer Science Volume: 109 Issue: 6 Pages: 2003-2012
  • DOI: 10.1111/cas.13608
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Control of PD-L1 expression by miR-140/142/340/383 and oncogenic activation of the OCT4?miR-18a pathway in cervical cancer (2018)
  • Author(s): Dong Peixin、Xiong Ying、Yu Jiehai、Chen Lin、Tao Tang、Yi Song、Hanley Sharon J. B.、Yue Junming、Watari Hidemichi、Sakuragi Noriaki
  • Journal Title: Oncogene Volume: 37 Issue: 39 Pages: 5257-5268
  • DOI: 10.1038/s41388-018-0347-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] miR-34a, miR-424 and miR-513 inhibit MMSET expression to repress endometrial cancer cell invasion and sphere formation (2018)
  • Author(s): Dong Peixin、Xiong Ying、Yue Junming、Hanley Sharon J.B.、Watari Hidemichi
  • Journal Title: Oncotarget Volume: 9 Issue: 33 Pages: 23253-23263
  • DOI: 10.18632/oncotarget.25298
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] miR-363 confers taxane resistance in ovarian cancer by targeting the Hippo pathway member, LATS2 (2018)
  • Author(s): Mohamed Z, Hassan M. K, Okasha S, Mitamura T, Keshk S, Konno Y, Kato T, El-Khamisy S. F, Ohba Y, Watari H
  • Journal Title: Oncotarget Volume: 9 Issue: 53 Pages: 30053-65
  • DOI: 10.18632/oncotarget.25698
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] miR-203 inhibits ovarian tumor metastasis by targeting BIRC5 and attenuating the TGFβ pathway (2018)
  • Author(s): Wang Baojin、Li Xia、Zhao Guannan、Yan Huan、Dong Peixin、Watari Hidemichi、Sims Michelle、Li Wei、Pfeffer Lawrence M、Guo Yuqi、Yue Junming
  • Journal Title: Journal of Experimental & Clinical Cancer Research Volume: 37 Issue: 1 Pages: 235-240
  • DOI: 10.1186/s13046-018-0906-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lentiviral vector mediated-ASAP1 expression promotes epithelial to mesenchymal transition in ovarian cancer cells (2018)
  • Author(s): Zhang Tao、Zhao Guannan、Yang Chuanhe、Dong Peixin、Watari Hidemichi、Zeng Lin、Pfeffer Lawrence、Yue Junming
  • Journal Title: Oncology Letters Volume: 15 Pages: 4432-4438
  • DOI: 10.3892/ol.2018.7834
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Book] 今日の治療指針 (2017)
  • Author(s): 渡利英道
  • Total Pages: 2100
  • Publisher: 医学書院