Development of control method for hepatocellular carcinoma circulating tumor cells based on immunity-related gene polymorphism analysis

• Project/Area Number: 15K10166
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Hiroshima University
• Principal Investigator: Kobayashi Tsuyoshi 広島大学, 医歯薬保健学研究科(医), 特任講師 (50528007)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肝細胞癌 / 循環腫瘍細胞 / 門脈浸潤 / 転移 / 肝切除

Outline of Final Research Achievements

The purpose of this study was to develop a detection method of circulating tumor cells (CTC) specific to hepatocellular carcinoma and construct a system to accurately predict metastasis of hepatocellular carcinoma, and to establish a control method of CTC based on immune-related gene polymorphism analysis.
We established Glypican-3 (GPC3) positive CTC detection method using the magnetic cell separation system. Among 88 HCC resected cases, 53 cases (60.2%) were CTC positive and CTC positive (p<0.001) was an independent risk factor for portal vein invasion. CTC positive was also an independent risk factor for relapse-free survival (p=0.029). GPC3-CTC reflects portal vein invasion and postoperative recurrence and is a reasonable candidate as a target for postoperative adjuvant therapy.

Research Products

• [Journal Article] Significance of the Glasgow Prognostic Score for patients with colorectal liver metastasis (2017)
  • Author(s): Okimoto Sho、Kobayashi Tsuyoshi、Tashiro Hirotaka、Kuroda Shintaro、Ishiyama Kohei、Ide Kentaro、Abe Tomoyuki、Hashimoto Masakazu、Iwako Hiroshi、Hamaoka Michinori、Honmyo Naruhiko、Yamaguchi Megumi、Ohdan Hideki
  • Journal Title: International Journal of Surgery Volume: 42 Pages: 209-214
  • DOI: 10.1016/j.ijsu.2017.04.068
  • Peer Reviewed
• [Journal Article] Prediction of recurrence following hepatectomy in patients with hepatitis C virus infection-related hepatocellular carcinoma who achieved a sustained virological response. (2017)
  • Author(s): Okimoto S, Kobayashi T, Kuroda S et al.
  • Journal Title: Hepatol Res Volume: in press Issue: 11 Pages: 1186-1195
  • DOI: 10.1111/hepr.12896
  • Peer Reviewed
• [Journal Article] 3D printing model of the intrahepatic vessels for navigation during anatomical resection of hepatocellular carcinoma (2017)
  • Author(s): Kuroda Shintaro、Kobayashi Tsuyoshi、Ohdan Hideki
  • Journal Title: International Journal of Surgery Case Reports Volume: 41 Pages: 219-222
  • DOI: 10.1016/j.ijscr.2017.10.015
  • Peer Reviewed
• [Journal Article] Application of endobronchial ultrasonography in laparoscopic liver segmentectomy in an animal model (2017)
  • Author(s): Abe Tomoyuki、Kobayashi Tsuyoshi、Shimizu Seiichi、Hamaoka Michinori、Iwako Hiroshi、Hashimoto Masakazu、Mikuriya Yoshihiro、Kuroda Shintaro、Tashiro Hirotaka、Ohdan Hideki
  • Journal Title: Asian Journal of Endoscopic Surgery Volume: 10 Issue: 2 Pages: 209-212
  • DOI: 10.1111/ases.12346
  • Peer Reviewed
• [Journal Article] Glasgow Prognostic Score and Prognosis After Hepatectomy for Hepatocellular Carcinoma (2017)
  • Author(s): Abe Tomoyuki、Tashiro Hirotaka、Kobayashi Tsuyoshi、Hattori Minoru、Kuroda Shintaro、Ohdan Hideki
  • Journal Title: World Journal of Surgery Volume: 41 Issue: 7 Pages: 1860-1870
  • DOI: 10.1007/s00268-017-3909-7
  • Peer Reviewed
• [Journal Article] Perioperative Red Blood Cell Transfusion Is Associated with Poor Long-term Survival in Pancreatic Adenocarcinoma (2017)
  • Author(s): Abe, T. Amano, H. Hanada, K. Minami, T. Yonehara, S. Hattori, M. Kobayashi, T. Fukuda, T. Nakahara, M. Ohdan, H. Noriyuki, T.
  • Journal Title: Anticancer Research Volume: 37 Issue: 10 Pages: 5863-5870
  • DOI: 10.21873/anticanres.12031
  • Peer Reviewed
• [Journal Article] Evaluation of the risk factors and prognostic factors of hepatectomy for hepatocellular carcinoma in patients aged 80 years or more (2017)
  • Author(s): Hamaoka Michinori、Kobayashi Tsuyoshi、Ishiyama Kohei、Ohira Masahiro、Tahara Hiroyuki、Kuroda Shintaro、Iwako Hiroshi、Okimoto Sho、Honmyo Naruhiko、Ohdan Hideki
  • Journal Title: Journal of Hepato-Biliary-Pancreatic Sciences Volume: 24 Issue: 1 Pages: 58-64
  • DOI: 10.1002/jhbp.413
  • Peer Reviewed
• [Journal Article] Hepatectomy after down-staging of hepatocellular carcinoma with portal vein tumor thrombus using chemoradiotherapy: A retrospective cohort study (2017)
  • Author(s): Hamaoka Michinori、Kobayashi Tsuyoshi、Kuroda Shintaro、Iwako Hiroshi、Okimoto Sho、Kimura Tomoki、Aikata Hiroshi、Nagata Yasushi、Chayama Kazuaki、Ohdan Hideki
  • Journal Title: International Journal of Surgery Volume: 44 Pages: 223-228
  • DOI: 10.1016/j.ijsu.2017.06.082
  • Peer Reviewed
• [Journal Article] Predictive Independent Factors for Extrahepatic Metastasis of Hepatocellular Carcinoma Following Curative Hepatectomy (2017)
  • Author(s): HASHIMOTO MASAKAZU、KOBAYASHI TSUYOSHI、ISHIYAMA KOHEI、IDE KENTARO、OHIRA MASAHIRO、TAHARA HIROYUKI、KURODA SHINTARO、HAMAOKA MICHINORI、IWAKO HIROSHI、OKIMOTO SHO、HONMYO NARUHIKO、OHDAN HIDEKI
  • Journal Title: Anticancer Research Volume: 37 Issue: 5 Pages: 2625-2631
  • DOI: 10.21873/anticanres.11609
  • Peer Reviewed
• [Journal Article] Viability of Airborne Tumor Cells during Excision by Ultrasonic Device (2017)
  • Author(s): Hashimoto Masakazu、Kobayashi Tsuyoshi、Tashiro Hirotaka、Kuroda Shintaro、Mikuriya Yoshihiro、Abe Tomoyuki、Tanaka Yuka、Ohdan Hideki
  • Journal Title: Surgery Research and Practice Volume: 2017 Pages: 1-5
  • DOI: 10.1155/2017/4907576
  • Peer Reviewed
• [Journal Article] Clinical characteristics and prognosis of non-B, non-C hepatocellular carcinoma: The impact of patient sex on disease-free survival - A retrospective cohort study (2017)
  • Author(s): Hashimoto Masakazu、Tashiro Hirotaka、Kobayashi Tsuyoshi、Kuroda Shintaro、Hamaoka Michinori、Ohdan Hideki
  • Journal Title: International Journal of Surgery Volume: 39 Pages: 206-213
  • DOI: 10.1016/j.ijsu.2017.01.110
  • Peer Reviewed
• [Journal Article] Influence of higher BMI for hepatitis B- and C-related hepatocellular carcinomas (2017)
  • Author(s): Hashimoto Masakazu、Tashiro Hirotaka、Kobayashi Tsuyoshi、Kuroda Shintaro、Hamaoka Michinori、Ohdan Hideki
  • Journal Title: Langenbeck's Archives of Surgery Volume: 402 Issue: 5 Pages: 745-755
  • DOI: 10.1007/s00423-017-1589-2
  • Peer Reviewed
• [Journal Article] Comparison of anatomic and non-anatomic hepatic resection for hepatocellular carcinoma (2017)
  • Author(s): Kaibori M、Kon M、Kitawaki T、Kawaura T、Hasegawa K、Kokudo N、Ariizumi S、Beppu T、Ishizu H、Kubo S、Kamiyama T、Takamura H、Kobayashi T、Kim DS、Wang HJ、Kim JM、Han DH、Park SJ、Kang KJ、Hwang S、Roh Y、You YK、Joh JW、Yamamoto M
  • Journal Title: Journal of Hepato-Biliary-Pancreatic Sciences Volume: 24 Issue: 11 Pages: 616-626
  • DOI: 10.1002/jhbp.502
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Periostin promotes malignant potential by induction of epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma (2017)
  • Author(s): Mino M, Kanno K, Okimoto K, Sugiyama A, Kishikawa N, Kobayashi T, Ono J, Izuhara K, Kobayashi T, Ohigashi T, Ohdan H, Tazuma S
  • Journal Title: Hepatol Commun Volume: 1 Issue: 10 Pages: 1099-1109
  • DOI: 10.1002/hep4.1114
  • Peer Reviewed / Open Access
• [Journal Article] Effect of Fc-γ Receptor Polymorphism on Rituximab-Mediated B Cell Depletion in ABO-Incompatible Adult Living Donor Liver Transplantation (2017)
  • Author(s): Sakai Hiroshi、Tanaka Yuka、Tazawa Hirofumi、Shimizu Seiichi、Verma Sapana、Ohira Masahiro、Tahara Hiroyuki、Ide Kentaro、Ishiyama Kohei、Kobayashi Tsuyoshi、Onoe Takashi、Ohdan Hideki
  • Journal Title: Transplantation Direct Volume: 3 Issue: 6 Pages: e164-e164
  • DOI: 10.1097/txd.0000000000000683
  • Peer Reviewed
• [Journal Article] MELD and Child-Pugh Scores Are Related to Immune Status of Intrahepatic Natural Killer Cells in Liver Transplant Candidates. (2017)
  • Author(s): Tanimine N, Tanaka Y, Abe T, Piao J, Ishiyama K, Kobayashi T, Ide K, Ohira M, Tahara H, Shimizu S, Saeki Y, Sakai H, Yano T, Ohdan H.
  • Journal Title: Transplant Proceedings Volume: 49 Issue: 1 Pages: 98-101
  • DOI: 10.1016/j.transproceed.2016.11.020
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] h-prune affects anaplastic thyroid cancer invasion and metastasis. (2016)
  • Author(s): Nambu J, Kobayashi T, Hashimoto M, et al.
  • Journal Title: Oncol Rep Volume: 35 Issue: 6 Pages: 3445-52
  • DOI: 10.3892/or.2016.4759
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] h-Prune is associated with poor prognosis and epithelial-mesenchymal transition in patients with colorectal liver metastases. (2016)
  • Author(s): Hashimoto M, Kobayashi T, Tashiro H, et al.
  • Journal Title: Int J Cancer Volume: 139 Issue: 4 Pages: 812-23
  • DOI: 10.1002/ijc.30118
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Efficacy and Feasibility of Salvage Living Donor Liver Transplantation after Initial Liver Resection in Patients with Hepatocellular Carcinoma. (2016)
  • Author(s): Abe, T., Tashiro, H., Teraoka, Y., Hattori, M., Tanimine, N., Kuroda, S., Tahara, H., Ohira, M., Tanaka, Y., Kobayashi, T., et al.
  • Journal Title: Digestive surgery Volume: 33 Issue: 1 Pages: 8-14
  • DOI: 10.1159/000441397
  • Peer Reviewed
• [Journal Article] Fatty liver creates a pro-metastatic microenvironment for hepatocellular carcinoma through activation of hepatic stellate cells. (2015)
  • Author(s): Mikuriya, Y., Tashiro, H., Kuroda, S., Nambu, J., Kobayashi, T., Amano, H., Tanaka, Y., and Ohdan, H.
  • Journal Title: International journal of cancer Volume: 136 Issue: 4
  • DOI: 10.1002/ijc.29096
  • Peer Reviewed
• [Presentation] 肝細胞癌における循環腫瘍細胞の検出とNK 細胞ライセンシング (2017)
  • Author(s): 小林剛、谷峰直樹、浜岡道則、田中友加、 大段秀樹
  • Organizer: 第117 回日本外科学会定期学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2017-04-27
• [Presentation] 肝細胞癌患者においてGlypican3陽性CTC は門 脈侵襲の予測因子になる (2017)
  • Author(s): 浜岡道則、小林剛、田中友加、石山宏平、 井手健太郎、大平真裕、田原裕之、黒田慎太郎、 清水誠一、岩子寛、沖本将、本明慈彦、山口恵美、 大段秀樹
  • Organizer: 第117 回日本外科学会定期学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2017-04-27
• [Presentation] 肝細胞癌における循環腫瘍細胞の検出とNK細胞ライセンシング (2017)
  • Author(s): 小林剛、谷峰直樹、浜岡道則、田中友加、大段秀樹
  • Organizer: 第117回日本外科学会定期学術集会
• [Presentation] Anatomical hepatectomy with the midline incision for right-sided liver tumors (2017)
  • Author(s): Kobayashi T, Okimoto S, Kuroda S, Hamaoka M, Shimizu S, Tahara H, Ohira M, Ide K, Ishiyama K, Ohdan H
  • Organizer: the 6th Biennial Congress of the Asian-Pacific Hepato-Pancreato-Biliary Association
  • Int'l Joint Research
• [Presentation] 肝機能からみたIntermediate stage肝細胞癌に対する肝切除の適応 (2017)
  • Author(s): 小林剛、黒田慎太郎、浜岡道則、井手健太郎、大平真裕、田原裕之、清水誠一、沖本将、本明慈彦、山口恵美、 相方浩、茶山一彰、大段秀樹
  • Organizer: 第53回日肝癌研究会
• [Presentation] 肝細胞癌患者においてGlypican3陽性CTCは門脈侵襲の予測因子になる (2017)
  • Author(s): 浜岡道則、小林剛、田中友加、石山宏平、井手健太郎、大平真裕、田原裕之、黒田慎太郎、清水誠一、岩子寛、沖本将、本明慈彦、山口恵美、大段秀樹
  • Organizer: 第117回日本外科学会定期学術集会
• [Presentation] Glypican3を用いたHCCにおけるCTC検出系の確立とその意義 (2017)
  • Author(s): 浜岡道則、小林剛、田中友加、石山宏平、井手健太郎、大平真裕、田原裕之、黒田慎太郎、本明慈彦、大段秀樹
  • Organizer: 第72回日本消化器外科学会総会
• [Presentation] 肝がん再発予防法の確立に向けた取り組み (2017)
  • Author(s): 小林剛、井手健太郎、大平真裕、田原裕之、黒田慎太郎、清水誠一、浜岡道則、大段秀樹
  • Organizer: 第79回日本臨床外科学会総会
  • Invited
• [Presentation] 門脈腫瘍栓合併肝癌に対する肝動注化学放射線療法とconversion surgery (2017)
  • Author(s): 小林剛、濵岡道則、田原裕之、真島宏聡、山口恵美、本明慈彦、沖本将、清水誠一、黒田慎太郎、大平真裕、井手健太郎、大段秀樹
  • Organizer: 第79回日本臨床外科学会総会
  • Invited
• [Presentation] 門脈本幹腫瘍栓を伴う肝細胞癌に対する化学放射線療法後の肝中央二区域切除 (2015)
  • Author(s): 小林剛, 濱岡道則, 田代裕尊, 石山宏平, 井手健太郎, 大平真裕, 田原裕之, 黒田慎太郎, 橋本昌和, 岩子寛, 大段秀樹
  • Organizer: 第27回日本肝胆膵外科学会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-11
• [Remarks] Gastroenterological and Transplant Surgery
  • URL: http://home.hiroshima-u.ac.jp/home2ge/en/
• [Remarks]
  • URL: http://home.hiroshima-u.ac.jp/home2ge/