Establishing the molecular pathology-based subclassification of hepatocellular carcinoma.

• Project/Area Number: 26293081
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Keio University
• Principal Investigator: SAKAMOTO Michiie 慶應義塾大学, 医学部, 教授 (40221270)
• Research Collaborator: FUKUMA Mariko ; YAMAZAKI Ken ; EFFENDI Kathryn
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000); Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
• Keywords: 病理学 / 肝細胞癌 / シグナル伝達 / サブクラス / ERK / 癌

Outline of Final Research Achievements

By analyzing cell signaling features and phenotype immunohistochemically, a new subclassification of hepatocellular carcinoma (HCC) that reflects the degree of malignancy was established. Activated MAPK signaling or overexpression of Glypican 3 as therapeutic target candidates were shown in biliary/stem cell marker-positive HCCs. The use of MRI to diagnose HCC with activated WNT signaling was also revealed. These findings are expected to be applied in the clinical practice.

Research Products

• [Journal Article] Serum Wisteria Floribunda Agglutinin-Positive Sialylated Mucin 1 as a Marker of Progenitor/Biliary Features in Hepatocellular Carcinoma. (2017)
  • Author(s): Tamaki N, Kuno A, Matsuda A, Tsujikawa H, Yamazaki K, Yasui Y, Tsuchiya K, Nakanishi H, Itakura J, Korenaga M, Mizokami M, Kurosaki M, Sakamoto M, Narimatsu H, Izumi N.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 244-244
  • DOI: 10.1038/s41598-017-00357-8
  • Peer Reviewed / Open Access
• [Journal Article] Pathological Findings of Nonalcoholic Steatohepatitis and Nonalcoholic Fatty Liver Disease. (2017)
  • Author(s): Sakamoto M, Tsujikawa H, Effendi K, Ojima H, Harada K, Zen Y, Kondo F, Nakano M, Kage M, Sumida Y, Hashimoto E, Yamada G, Okanoue T, Koike K.
  • Journal Title: Pathology International Volume: 67 Issue: 1 Pages: 1-7
  • DOI: 10.1111/pin.12485
  • Peer Reviewed / Open Access
• [Journal Article] Elastin Fiber Accumulation in Liver Correlates with the Development of Hepatocellular Carcinoma. (2016)
  • Author(s): Yasui Y, Abe T, Kurosaki M, Higuchi M, Komiyama Y, Yoshida T, Hayashi T, Kuwabara K, Takaura K, Nakakuki N, Takada H, Tamaki N, Suzuki S, Nakanishi H, Tsuchiya K, Itakura J, Takahashi Y, Hashiguchi A, Sakamoto M, Izumi N.
  • Journal Title: PLoS One Volume: 11 Issue: 4 Pages: e0154558-e0154558
  • DOI: 10.1371/journal.pone.0154558
  • Peer Reviewed / Open Access
• [Journal Article] Molecular pathology and malignancy of hepatocellular carcinoma (2016)
  • Author(s): Kawaida M, Tsujikawa H, Sakamoto M.
  • Journal Title: Nippon Shokakibyo Gakkai Zasshi Volume: 113 Issue: 5 Pages: 761-766
  • DOI: 10.11405/nisshoshi.113.761
  • NAID: 130005150382
  • ISSN: 0446-6586, 1349-7693
  • Peer Reviewed
• [Journal Article] Early hepatocellular carcinoma with high-grade atypia in small vaguely nodular lesions. (2016)
  • Author(s): Ojima H, Masugi Y, Tsujikawa H, Emoto K, Fujii-Nishimura Y, Hatano M, Kawaida M, Itano O, Kitagawa Y, Sakamoto M.
  • Journal Title: Cancer Sci. Volume: 107 Issue: 4 Pages: 543-50
  • DOI: 10.1111/cas.12893
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Immunohistochemical molecular analysis indicates hepatocellular carcinoma subgroups that reflect tumor aggressiveness. (2016)
  • Author(s): Tsujikawa H, Masugi Y, Yamazaki K, Itano O, Kitagawa Y, Sakamoto M.
  • Journal Title: Hum Pathol. Volume: 50 Pages: 24-33
  • DOI: 10.1016/j.humpath.2015.10.014
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Comprehensive Immune Profiling of Lung Adenocarcinomas Reveals Four Immunosubtypes with Plasma Cell Subtype a Negative Indicator. (2016)
  • Author(s): Kurebayashi Y, Emoto K, Hayashi Y, Kamiyama I, Ohtsuka T, Asamura H, Sakamoto M.
  • Journal Title: Cancer Immunol Res. Volume: 4(3) Issue: 3 Pages: 234-237
  • DOI: 10.1158/2326-6066.cir-15-0214
  • Peer Reviewed
• [Journal Article] Overexpression of adenylate cyclase-associated protein 2 is a novel prognostic marker in malignant melanoma. (2015)
  • Author(s): Masugi Y, Tanese K, Emoto K, Yamazaki K, Effendi K, Funakoshi T, Mori M, Sakamoto M.
  • Journal Title: Pathol Int. Volume: 65 Issue: 12 Pages: 627-34
  • DOI: 10.1111/pin.12351
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] OATP1B3 expression is strongly associated with Wnt/β-catenin signalling and represents the transporter of gadoxetic acid in hepatocellular carcinoma. (2014)
  • Author(s): Ueno A, Masugi Y, Yamazaki K, Komuta M, Effendi K, Tanami Y, Tsujikawa H, Tanimoto A, Okuda S, Itano O, Kitagawa Y, Kuribayashi S, Sakamoto M.
  • Journal Title: Journal of Hepatology Volume: 61 Issue: 5 Pages: 1080-1087
  • DOI: 10.1016/j.jhep.2014.06.008
  • Peer Reviewed