Integrative omics analysis for novel therapeutic target molecules for soft tissue sarcoma of rare cancer

• Project/Area Number: 16K10874
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: 独立行政法人国立病院機構(東京医療センター臨床研究センター) (2017-2018); Keio University (2016)
• Principal Investigator: Morioka Hideo 独立行政法人国立病院機構(東京医療センター臨床研究センター), 政策医療企画研究部, 医長 (10230096)
• Co-Investigator(Kenkyū-buntansha): 菊田 一貴 東京歯科大学, 歯学部, 非常勤講師 (30383798) ; 堀内 圭輔 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 整形外科学, 講師 (30327564)
• 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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 希少がん / 軟部肉腫 / 分子標的治療 / オミクス研究 / 化学療法 / 分子標的薬 / プロテオーム解析 / 遺伝子解析

Outline of Final Research Achievements

The purpose of this study was to clarify the pathophysiology and molecular mechanism of soft tissue sarcoma, and to expand the indications of existing therapeutic agents and to open the way to the development of new therapeutic agents. Surgical treatment is the first choice for soft tissue sarcoma, but if local recurrence or distant metastasis occurs, it will depend on chemotherapy as a systemic treatment. However, because soft tissue sarcoma is a rare cancer, drug development is delayed compared to other carcinomas. In this study, we aimed to expand the application of existing molecular target drugs, conduct research using the method of omics research, search for new target molecules for soft tissue sarcoma. From analysis of many clinical specimens, in highly invasive myxofibrosarcoma, the molecule DCBLD2 has been shown to be a biomarker for invasion and metastasis.

Academic Significance and Societal Importance of the Research Achievements

最先端の網羅的解析技術により、治療抵抗性の高悪性粘液線維肉腫の病態に深く関わるDCBLD2という分子を同定した。DCBLD2はすべての軟部肉腫の病態に関連する可能性がある重要な分子（タンパク質）であり、希少がんであるが故に開発が遅れていた軟部肉腫に対する新規治療薬開発や既存薬剤の適応拡大に役立つと考えられる。今後、本分子（タンパク質）を制御する新規治療薬開発と臨床応用に研究を発展させていきたいと考えている。希少がんである軟部肉腫に対して行われた本研究は、限られた治療法の中で苦しむ軟部肉腫患者の治療成績向上に資する成果と考えている。

Research Products

• [Journal Article] A serum microRNA classifier for the diagnosis of sarcomas of various histological subtypes. (2019)
  • Author(s): Asano N, Matsuzaki J, Ichikawa M, Kawauchi J, Takizawa S, Aoki Y, Sakamoto H, Yoshida A, Kobayashi E, Tanzawa Y, Nakayama R, Morioka H, Matsumoto M, Nakamura M, Kondo T, Kato K, Tsuchiya N, Kawai A, Ochiya T
  • Journal Title: Nature Communications Volume: 10 Issue: 1 Pages: 1299-1299
  • DOI: 10.1038/s41467-019-09143-8
  • Peer Reviewed / Open Access
• [Journal Article] Reconstruction using a constrained-type hip tumor prosthesis after resection of malignant periacetabular tumors: A study by the Japanese Musculoskeletal Oncology Group (JMOG). (2018)
  • Author(s): Ogura K, Susa M, Morioka H, Matsumine A, Ishii T, Hamada K, Ueda T, Kawai A
  • Journal Title: J Surg Oncol Volume: 印刷中 Issue: 7 Pages: 1455-1463
  • DOI: 10.1002/jso.25005
  • Peer Reviewed / Open Access
• [Journal Article] Giant Cell Tumors of the Bone: Changes in Image Features after Denosumab Administration (2018)
  • Author(s): Oguro S, Okuda S, Sugiura H, Matsumoto S, Sasaki A, Susa M, Morioka H, Jinzaki M.
  • Journal Title: Magnetic Resonance in Medical Sciences Volume: 17 Issue: 4 Pages: 325-330
  • DOI: 10.2463/mrms.mp.2017-0072
  • NAID: 130007496594
  • ISSN: 1347-3182, 1880-2206
  • Peer Reviewed
• [Journal Article] Preoperatively determining the margins of subcutaneous malignant soft tissue tumours using contrast-enhanced ultrasonography (2017)
  • Author(s): Oguro Sota、Kikuta Kazutaka、Sasaki Aya、Okuma Kiyoshi、Matsumoto Shunsuke、Sugiura Hiroaki、Morioka Hideo、Nakamura Masaya、Matsumoto Morio、Jinzaki Masahiro
  • Journal Title: Journal of Medical Ultrasonics Volume: 45 Issue: 2 Pages: 385-388
  • DOI: 10.1007/s10396-017-0826-1
  • Peer Reviewed
• [Journal Article] Wide-spread ignorance on the treatment of subcutaneous malignant tumors; a questionnaire-based study (2017)
  • Author(s): Kikuta Kazutaka、Nakayama Robert、Yamaguchi Sayaka、Nishiwaki Yuuji、Susa Michiro、Nishimoto Kazumasa、Horiuchi Keisuke、Nakamura Masaya、Matsumoto Morio、Morioka Hideo
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 48 Issue: 2 Pages: 130-134
  • DOI: 10.1093/jjco/hyx184
  • Peer Reviewed
• [Journal Article] Impact of geriatric factors on surgical and prognostic outcomes in elderly patients with soft-tissue sarcoma. (2017)
  • Author(s): Tsuda Y, Ogura K, Kobayashi E, Hiruma T, Iwata S, Asano N, Kawai A, Chuman H, Ishii T, Morioka H, Kobayashi H, Kawano H.
  • Journal Title: Jpn J Clin Oncol Volume: 2017/2/15 Issue: 5 Pages: 1-8
  • DOI: 10.1093/jjco/hyx016
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of Trabectedin in Patients with Advanced Translocation‐Related Sarcomas: Pooled Analysis of Two Phase II Studies (2017)
  • Author(s): Takahashi Mitsuru、Takahashi Shunji、Araki Nobuhito、Sugiura Hideshi、Ueda Takafumi、Yonemoto Tsukasa、Morioka Hideo、Hiraga Hiroaki、Hiruma Toru、Kunisada Toshiyuki、Matsumine Akihiko、Shimura Masashi、Kawai Akira
  • Journal Title: The Oncologist Volume: 22 Issue: 8 Pages: 979-988
  • DOI: 10.1634/theoncologist.2016-0064
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Factors associated with the decision of operative procedure for proximal femoral bone metastasis: Questionnaire survey to institutions participating the Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group (2017)
  • Author(s): Araki Nobuhito、Tanaka Kazuhiro、Katagiri Hirohisa、Kunisada Toshiyuki、Hiruma Toru、Hiraga Hiroaki、Morioka Hideo、Nishida Yoshihiro、Abe Satoshi、Watanuki Munenori、Morii Takeshi、Sugiura Hideshi、Yoshida Yukihiro、Yokoyama Koichiro、Shimose Shoji、Iwamoto Yukihide
  • Journal Title: Journal of Orthopaedic Science Volume: 22 Issue: 5 Pages: 938-945
  • DOI: 10.1016/j.jos.2017.05.012
  • Peer Reviewed
• [Journal Article] Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is a novel biomarker of myxofibrosarcoma invasion identified by global protein expression profiling (2017)
  • Author(s): Kikuta Kazutaka、Kubota Daisuke、Yoshida Akihiko、Qiao Zhiwei、Morioka Hideo、Nakamura Masaya、Matsumoto Morio、Chuman Hirokazu、Kawai Akira、Kondo Tadashi
  • Journal Title: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics Volume: 1865 Issue: 9 Pages: 1160-1166
  • DOI: 10.1016/j.bbapap.2017.06.023
  • NAID: 130007498586
  • Peer Reviewed / Open Access
• [Journal Article] Preoperative evaluation of renal cell carcinoma patients with bone metastases on risks for blood loss, performance status and lethal event (2017)
  • Author(s): Yoshiyama Akira、Morii Takeshi、Susa Michiro、Morioka Hideo、Kobayashi Eisuke、Asano Naofumi、Mori Tomoaki、Anazawa Ukei、Watanabe Itsuo、Takeuchi Katsuhito、Kushima Yu、Aoyagi Takayuki、Ichimura Shoichi
  • Journal Title: Journal of Orthopaedic Science Volume: 22 Issue: 5 Pages: 924-930
  • DOI: 10.1016/j.jos.2017.07.006
  • Peer Reviewed
• [Journal Article] Metastasis of Renal Cell Carcinoma to the Trapezium (2017)
  • Author(s): Nakagawa Rumi、Susa Michiro、Nakayama Robert、Watanabe Itsuo、Horiuchi Keisuke、Toyama Yoshiaki、Nakamura Masaya、Matsumoto Morio、Morioka Hideo
  • Journal Title: The Journal of Hand Surgery (Asian-Pacific Volume) Volume: 22 Issue: 02 Pages: 262-265
  • DOI: 10.1142/s0218810417720212
  • Peer Reviewed
• [Journal Article] Extraskeletal Chondroma of the Index Finger: A Case Report (2017)
  • Author(s): Saito Masato、Nishimoto Kazumasa、Nakayama Robert、Kikuta Kazutaka、Nakamura Masaya、Matsumoto Morio、Morioka Hideo
  • Journal Title: Case Reports in Oncology Volume: 10 Issue: 2 Pages: 479-484
  • DOI: 10.1159/000477237
  • Peer Reviewed / Open Access
• [Journal Article] Results of sub-analysis of a phase 2 study on trabectedin treatment for extraskeletal myxoid chondrosarcoma and mesenchymal chondrosarcoma. (2016)
  • Author(s): Morioka H, Takahashi S, Araki N, Sugiura H, Ueda T, Takahashi M, Yonemoto T, Hiraga H, Hiruma T, Kunisada T, Matsumine A, Susa M, Nakayama R, Nishimoto K, Kikuta K, Horiuchi K, Kawai A
  • Journal Title: BMC Cancer Volume: 16 Issue: 1 Pages: 479-479
  • DOI: 10.1186/s12885-016-2511-y
  • Peer Reviewed / Open Access
• [Journal Article] CT guided cryoablation for locally recurrent or metastatic bone and soft tissue tumor: initial experience. (2016)
  • Author(s): Susa M, Kikuta K, Nakayama R, Nishimoto K, Horiuchi K, Oguro S, Inoue M, Yashiro H, Nakatsuka S, Nakamura M, Matsumoto M, Chiba K, Morioka H.
  • Journal Title: BMC Cancer. Volume: 16 Pages: 798-798
  • Peer Reviewed / Open Access
• [Journal Article] Feasibility and efficacy of gemcitabine and docetaxel combination chemotherapy for bone and soft tissue sarcomas: multi-institutional retrospective analysis of 134 patients. (2016)
  • Author(s): Tanaka K, Joyama S, Chuman H, Hiraga H, Morioka H, Yoshikawa H, Hosaka M, Takahashi M, Kubo T, Hatano H, Kaya M, Toguchida J, Nishida Y, Nagano A, Tsumura H, Iwamoto Y.
  • Journal Title: World J Surg Oncol. Volume: 14 Pages: 306-306
  • NAID: 120005997852
  • Peer Reviewed / Open Access
• [Journal Article] Diagnosis of extraskeletal myxoid chondrosarcoma in the thigh using EWSR1-NR4A3 gene fusion: a case report. (2016)
  • Author(s): Kobayashi H, Kikuta K, Sekita T, Susa M, Nishimoto K, Sasaki A, Kameyama K, Sugita S, Hasegawa T, Nakamura M, Matsumoto M, Morioka H.
  • Journal Title: J Med Case Rep. Volume: 10 Pages: 321-321
  • Peer Reviewed / Open Access
• [Journal Article] Hibernoma Showing High Uniform Accumulation on an 18F-Fluorodeoxyglucose Positron Emission Tomography Scan: A Case Report. (2016)
  • Author(s): Kamata Y, Kikuta K, Susa M, Nishimoto K, Sasaki A, Kameyama K, Murakami K, Nakamura M, Matsumoto M, Morioka H.
  • Journal Title: Case Rep Oncol. Volume: 9 Pages: 427-431
  • Peer Reviewed / Open Access
• [Presentation] Treatment of soft tissue sarcomas in patients age 80 years or older (2018)
  • Author(s): Susa M, Kobayashi E, Horiuchi K, Nakayama R, Watanabe I, Morioka H, Kawai A, Chiba K
  • Organizer: 12th Asia Pacific Musculoskeletal Tumor Society Meeting
  • Int'l Joint Research
• [Presentation] The effectiveness of denosumab for lung metastases of giant dell tumor of bone. (2018)
  • Author(s): Anazawa U, Watanabe I, Morioka H, Susa M, Kikuta K, Nakayama R
  • Organizer: 12th Asia Pacific Musculoskeletal Tumor Society Meeting
  • Int'l Joint Research
• [Presentation] Spontaneous regression of soft tissue sarcoma. (2018)
  • Author(s): Susa M, Horiuchi K, Saito M, Sato C, Nakayama R, Morioka H, Chiba K
  • Organizer: Conective Tissue Oncology Society 2018 Annual Meeting
  • Int'l Joint Research
• [Presentation] TNIK is a novel molecular target for osteosarcoma treatment and controls osteosarcoma cell fate. (2018)
  • Author(s): Hirozane T, Masuda M, Goto N, Sugano T, Asano N, Kobayashi E, Kawa A, Horiuchi K, Matsumoto M, Nakamura M, Sawa M, Morioka H, Nakayama R, Yamada T
  • Organizer: Conective Tissue Oncology Society 2018 Annual Meeting
  • Int'l Joint Research
• [Presentation] 蛍光二次元電気泳動法を用いたプロテオミクス解析により同定した粘液線維肉腫浸潤性評価バイオマーカーDCBLD2. (2018)
  • Author(s): 菊田 一貴, 窪田 大介, 吉田 朗彦, 森岡 秀夫, 中村 雅也, 松本 守雄, 川井 章, 近藤 格
  • Organizer: 第33回日本整形外科学会基礎学術集会
• [Presentation] 浸潤性発育を示す腫瘍に対する至適切除範囲 浸潤性軟部腫瘍の治療成績向上を目指した診断治療戦略 粘液線維肉腫を中心に. (2018)
  • Author(s): 菊田 一貴, 中山 ロバート, 浅野 尚文, 吉田 朗彦, 小黒 草太, 佐々木 文, 森岡 秀夫, 近藤 格, 川井 章, 中村 雅也, 松本 守雄
  • Organizer: 第51回日本整形外科学会骨・軟部腫瘍学術集会
• [Presentation] Efficacy of pazopanib for recurrent desmoid tumors in kamilial adenomatous polyposis patients. (2017)
  • Author(s): Susa M, Horiuchi K, Sekita T, Nakayama R, Morioka H, Chiba K
  • Organizer: 22nd Connective Tissue Oncology Society Meeting.
  • Int'l Joint Research
• [Presentation] Treatment of soft tissue sarcoma in patients age 80 year or older. (2017)
  • Author(s): Susa M, Horiuchi K, Sato C, Chiba K, Nakayama R, Watanabe I, Morioka H
  • Organizer: 22nd Connective Tissue Oncology Society Meeting.
  • Int'l Joint Research
• [Presentation] Discoidun, CUB and LCCL domain-containing protein 2 (DCBLD2) is a novel biomarker ofI myxofibrosarcoma invasion identified by global protein expression profiling. (2017)
  • Author(s): Kikuta K, Nakamura M, Matsumoto M, Kubota D, Kondo T, Yoshida A, Chuman H, Kawai A, Morioka H
  • Organizer: 22nd Connective Tissue Oncology Society Meeting.
  • Int'l Joint Research
• [Presentation] Forty-eight Cases of Leiomyosarcoma of Bone in Japan: A Multicenter Study from the Japanese Musculoskeletal Oncology Group. (2017)
  • Author(s): Mori T, Nakayama R, Endo M, Kobayashi E, Kawai A, Ueda T, Morioka H
  • Organizer: 19th International Society of Limb Salvage General Meeting.
  • Int'l Joint Research
• [Presentation] A Histological Positive Margin after Surgery Is Correlated with High Local Re-recurrence Rate in Patients with Recurrent Myxofibrosarcoma. (2017)
  • Author(s): Kikuta K, Nakayama R, Yoshida A, Sasaki A, Kameyama K, Chuuman H, Kawai A, Nakamura M, Matsumoto M, Morioka H
  • Organizer: 19th International Society of Limb Salvage General Meeting.
  • Int'l Joint Research
• [Presentation] Clinical Outcome of Ten Cases of Lipoblastoma. (2017)
  • Author(s): Sekita T, Nakayama R, Kikuta K, Horiuchi K, Susa M, Nakamura M, Matsumoto M, Morioka H
  • Organizer: 19th International Society of Limb Salvage General Meeting.
  • Int'l Joint Research
• [Presentation] Limb Salvage Surgery Using a Ceramic Spacer for Pediatric Bone Sarcomas. (2017)
  • Author(s): Saito M, Nakayama R, Susa M, Sekita T, Kikuta K, Nakamura M, Matsumoto M, Morioka H
  • Organizer: 19th International Society of Limb Salvage General Meeting. Kanazawa. Japan. 2017.
  • Int'l Joint Research
• [Presentation] Therapeutic Potential of a Novel TRAF2 and NCK-Interacting Protein Kinase Inhibitor against Osteosarcoma. (2017)
  • Author(s): Hirozane T, Masuda M, Goto N, Kobayashi E, Horiuchi K, Matsumoto M, Nakamura M, Morioka H, Sawa M, Yamada T
  • Organizer: 19th International Society of Limb Salvage General Meeting.
  • Int'l Joint Research
• [Presentation] Efficacy of FDG-PET in the Detection of Local Recurrence after Limb Salvage Surgery Using Metal Implants. (2017)
  • Author(s): Sekita T, Nakayama R, Kikuta K, Horiuchi K, Susa M, Nakamura M, Matsumoto M, Morioka H
  • Organizer: 19th International Society of Limb Salvage General Meeting.
  • Int'l Joint Research
• [Presentation] Three Cases of Recurrent Sacral Chordomas Treated with Computed Tomography-guided Percutaneous Cryoablation. (2017)
  • Author(s): Nakayama RT, Sekita T, Oguro S, Kikuta K, Yashiro H, Inoue M, Nakatsuka S, Nakamura M, Matsumoto M, Morioka H
  • Organizer: 19th International Society of Limb Salvage General Meeting.
  • Int'l Joint Research
• [Presentation] Preoperative Evaluation of Renal Cell Carcinoma Patients with Bone Metastases on Risks for Blood Loss, Performance Status and Lethal Event. (2017)
  • Author(s): Morii T, Yoshiyama A, Susa M, Morioka H, Kobayashi E, Asano N, Mori T, Anazawa U, Takeuchi K, Ichimura S
  • Organizer: 19th International Society of Limb Salvage General Meeting.
  • Int'l Joint Research
• [Presentation] Nomograms Predicting Distant Metastases and Overall Survival after Neoadjuvant Chemotherapy and Surgery for Patients with Non-metastatic Osteosarcoma: A Multi-institutional Study. (2017)
  • Author(s): Ogura K, Fujiwara T, Jeon DG, Cho WH, Hiraga H, Ishii T, Yonemoto T, Kamoda H, Ozaki T, Kozawa E, Nishida Y, Morioka H, Hiruma T, Kakunaga S, Ueda T, Araki N, Naka N, Tsuda Y, Kawano H, Kawai A
  • Organizer: 19th International Society of Limb Salvage General Meeting.
  • Int'l Joint Research
• [Book] 基本手術手技 良性骨腫瘍に対する手術・悪性骨腫瘍に対する手術， (2017)
  • Author(s): 森岡秀夫
  • Total Pages: 353
  • Publisher: 中山書店
  • ISBN: 9784521732558