胆管分化を示す肝癌の層別化

2023 Fiscal Year Research-status Report

• Project/Area Number: 22K06976
• Research Institution: The University of Tokyo
• Principal Investigator: 田中 麻理子 東京大学, 医学部附属病院, 講師 (50645710)
• Project Period (FY): 2022-04-01 – 2025-03-31
• Keywords: 胆管癌 / 肝癌 / KRAS / 混合型肝癌 / 病理組織学的形態 / 臨床的転帰

Outline of Annual Research Achievements

各種の癌病態において、遺伝子異常のもたらす臨床的動態と分子生物学的機序の同定や臨床的転帰と結び付いた亜分類は、疾病発生の理解や迅速かつ最適な治療介入を行う上で非常に重要である。しかしながら、胆管分化を示す肝癌は極めて予後不良であるにもかかわらず肝細胞癌に比して研究が進んでいない。本研究では、胆管分化を示す肝癌について、臨床的動態を反映した層別化を行うこと、またその発生起点を明らかにすることを目的とする。昨年度までに、本研究で収集・解析中の、胆管分化を示す肝癌の外科的切除症例の大規模なコホートを用い、肝内胆管癌ではKRAS変異陽性群がとりわけ予後不良な一群であること、そして、KRAS変異が蔟出形態をもたらすことで遠隔転移をきたしやすくなるため予後不良に寄与することを見出し論文報告している（Liver Int. 2022）。さらに本年度は、特異的融合遺伝子をもつ一群について、予後が良く、病理組織学的形態のspectrumが広いことを見出した（論文投稿後minor revision中）。今年度までの本研究の成果は、胆管分化を示す肝癌において、臨床的転帰とゲノム異常ならびに病理組織学的形態を結び付け、臨床的転帰に結び付いた亜分類を描出している点で個別化医療において非常に重要な意義がある。

Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

胆管分化を示す肝癌の解析症例総数の蓄積は順調に推移している。一方で、混合型肝癌については手術検体として得られる数が少なく、前向きな検体採取に関連した解析についてはやや遅れている。

Strategy for Future Research Activity

混合型肝癌症例の解析を進める。

Causes of Carryover

現在、今年度の成果について論文投稿後のrevise中であり、論文投稿関連費用として次年度使用予定である。

Research Products

• [Journal Article] Intraductal Papillary Mucinous Neoplasm Surveillance Leads to Early Diagnosis and Better Outcomes of Concomitant Cancer. (2024)
  • Author(s): Oyama H, Hamada T, Nakai Y, Tanaka M, Takagi K, Fukuda R, Hakuta R, Ishigaki K, Kanai S, Kawaguchi Y, Kurihara K, Nishio H, Noguchi K, Saito T, Sato T, Suzuki T, Suzuki Y, Takaoka S, Tange S, Takahara N, Hasegawa K, Ushiku T, Fujishiro M.
  • Journal Title: Ann Surg. Volume: - Pages: -
  • DOI: 10.1097/SLA.0000000000006268.
  • Peer Reviewed
• [Journal Article] Thick silk fibroin vascular graft: A promising tissue-engineered scaffold material for abdominal vein grafts in middle-sized mammals. (2024)
  • Author(s): Fukuda K, Kaneko J, Kiritani S, Sawa Y, Morito M, Tanaka M, Ushiku T, Cheng CJ, Tanaka T, Tanaka R, Asakura T, Kawaguchi Y, Akamatsu N, Hasegawa K.
  • Journal Title: Int J Artif Organs. Volume: 47 Pages: 190-197.
  • DOI: 10.1177/03913988241234547.
  • Peer Reviewed
• [Journal Article] Increased expression of TNFRSF14 and LIGHT in biliary epithelial cells of patients with primary sclerosing cholangitis. (2024)
  • Author(s): Kanai S, Fujiwara H, Mizuno S, Kishikawa T, Nakatsuka T, Hamada T, Tanaka M, Arita J, Nakai Y, Isayama H, Kasuga M, Tateishi R, Tateishi K, Ushiku T, Hasegawa K, Koike K, Fujishiro M.
  • Journal Title: Dig Liver Dis. Volume: 56 Pages: 305-311.
  • DOI: 10.1016/j.dld.2023.08.057.
  • Peer Reviewed
• [Journal Article] Post-operative mortality and recurrence patterns in pancreatic cancer according to KRAS mutation and CDKN2A, p53, and SMAD4 expression. (2023)
  • Author(s): Masugi Y, Takamatsu M, Tanaka M(Co-first author), Hara K, Inoue Y, Hamada T, Suzuki T, Arita J, Hirose Y, Kawaguchi Y, Nakai Y, Oba A, Sasahira N, Shimane G, Takeda T, Tateishi K, Uemura S, Fujishiro M, Hasegawa K, Kitago M, Takahashi Y, Ushiku T, Takeuchi K, Sakamoto M; GTK Pancreatic Cancer Study Group in Japan.
  • Journal Title: J Pathol Clin Res. Volume: 9 Pages: 339-353
  • DOI: 10.1002/cjp2.323.
  • Peer Reviewed
• [Journal Article] Systematic review of challenging issues in pathology of intraductal papillary mucinous neoplasms (2023)
  • Author(s): Wood LD, Adsay NV, Basturk O, Brosens LAA, Fukushima N, Hong SM, Kim SJ, Lee JW, Luchini C, Noe M, Pitman MB, Scarpa A, Singhi AD, Tanaka M, Furukawa T.
  • Journal Title: Pancreatology. Volume: 23 Pages: 878-891
  • DOI: 10.1016/j.pan.2023.08.002.
  • Peer Reviewed
• [Journal Article] Identification of odontogenic ameloblast associated as a novel target gene of the Wnt/β-catenin signaling pathway. (2023)
  • Author(s): Yamaguchi K, Horie C, Takane K, Ikenoue T, Nakagawa S, Isobe Y, Ota Y, Ushiku T, Tanaka M, Fujishiro J, Hoshino N, Arisue A, Nishizuka S, Aikou S, Shida D, Furukawa Y.
  • Journal Title: Cancer Sci. Volume: 114 Pages: 948-960.
  • DOI: 10.1111/cas.15657.
  • Peer Reviewed
• [Journal Article] Real-Time Fluorescence Imaging to Identify Cholangiocarcinoma in the Extrahepatic Biliary Tree Using an Enzyme-Activatable Probe. (2023)
  • Author(s): Takahashi R, Ishizawa T, Inagaki Y, Tanaka M, Ogasawara A, Kuriki Y, Fujita K, Kamiya M, Ushiku T, Urano Y, Hasegawa K.
  • Journal Title: Liver Cancer. Volume: 12 Pages: 590-602.
  • DOI: 10.1159/000530645.
  • Peer Reviewed
• [Journal Article] Clinical trajectory of intraductal papillary mucinous neoplasms progressing to pancreatic carcinomas during long-term surveillance: a prospective series of 100 carcinoma cases. (2023)
  • Author(s): Oyama H, Hamada T, Nakai Y, Tanaka M, Endo G, Hakuta R, Ishida K, Ishigaki K, Kanai S, Kurihara K, Saito T, Sato T, Suzuki T, Suzuki Y, Takaoka S, Tange S, Tokito Y, Takahara N, Ushiku T, Fujishiro M.
  • Journal Title: J Gastroenterol. Volume: 58 Pages: 1068-1080.
  • DOI: 10.1007/s00535-023-02028-0.
  • Peer Reviewed
• [Journal Article] Intraductal oncocytic papillary neoplasm of the pancreas: clinical and radiological features compared to those of intraductal papillary mucinous neoplasm. (2023)
  • Author(s): Nakaya M, Nakai Y, Takahashi M, Fukukura Y, Sato K, Kameda A, Tashiro Y, Kageyama S, Sofue K, Nakano T, Yoshimitsu K, Marugami N, Takeyama N, Tanaka M, Hasegawa K, Watadani T.
  • Journal Title: Abdom Radiol (NY). Volume: 48 Pages: 2483-2493.
  • DOI: 10.1007/s00261-023-03985-z.
  • Peer Reviewed
• [Journal Article] Clinical Outcomes of Intraductal Papillary Mucinous Neoplasms With Dilatation of the Main Pancreatic Duct. (2023)
  • Author(s): Hamada T, Oyama H, Nakai Y, Tange S, Arita J, Hakuta R, Ijichi H, Ishigaki K, Kanai S, Kawaguchi Y,Kogure H, Mizuno S, Saito K, Saito T, Sato T, Suzuki T, Takahara N, Tanaka M, Tateishi K, Ushiku T, Hasegawa K, Fujishiro M.
  • Journal Title: Clin Gastroenterol Hepatol. Volume: 1 Pages: 792-1801.
  • DOI: 10.1016/j.cgh.2023.01.032.
  • Peer Reviewed
• [Journal Article] Assessment of liver function-related mRNA expression and fluorescence imaging in outflow-obstructed regions in rats. (2023)
  • Author(s): Ito D, Kawaguchi Y, Inagaki Y, Ito K, Mihara Y, Kaneko J, Tanaka M, Fukayama M, Kokudo N, Hasegawa K.
  • Journal Title: Surg Today. Volume: 53 Pages: 513-521.
  • DOI: 10.1007/s00595-022-02588-3.
  • Peer Reviewed
• [Journal Article] Clinical utility of postablation liver tumor biopsy and possibility of gene mutation analysis. (2023)
  • Author(s): Nakatsuka T, Nakagawa H, Uchino K, Rokutan H, Tanaka M, Moriyama M, Fukumoto T, Yamada T, Wake T, Nakagomi R, Sato M, Minami T, Kudo Y, Ushiku T, Fujishiro M, Tateishi R.
  • Journal Title: Hepatol Res. Volume: 53 Pages: 1117-1125.
  • DOI: 10.1111/hepr.13944.
  • Peer Reviewed
• [Journal Article] Acute pancreatitis as the initial manifestation of acute myeloid leukemia with chromosome 16 rearrangements. (2023)
  • Author(s): Fukushima H, Morita K, Ikemura M, Tanaka M, Nakai Y, Maki H, Suzuki T, Mizuno S, Nakai Y, Kurokawa M.
  • Journal Title: Int J Hematol. Volume: 118 Pages: 381-387.
  • DOI: 10.1007/s12185-023-03580-4.
  • Peer Reviewed
• [Journal Article] Autoimmunity and immunodeficiency associated with monoallelic LIG4 mutations via haploinsufficiency. (2023)
  • Author(s): Jauch AJ, Bignucolo O, Seki S, Ghraichy M, Delmonte OM, Higgins R, Ghosh A, Nishizawa M, Tanaka M, Yamamoto H, Recher M et al.
  • Journal Title: J Allergy Clin Immunol. Volume: 152 Pages: 500-516.
  • DOI: 10.1016/j.jaci.2023.03.022.
  • Peer Reviewed
• [Journal Article] Lymphoproliferative disorder during temozolomide therapy; a representative case of a formidable complication and management challenges. (2023)
  • Author(s): Sato D, Takami H, Takayanagi S, Taoka K, Tanaka M, Matsuura R, Tanaka S, Saito N.
  • Journal Title: BMC Neurol. Volume: 23 Pages: 224
  • DOI: 10.1186/s12883-023-03274-8.
  • Peer Reviewed
• [Presentation] 膵胆道癌とがんゲノム医療の実際. (2024)
  • Author(s): 田中麻理子.
  • Organizer: 第113回日本病理学会総会
• [Presentation] 若年発症膵癌の臨床病理学的特徴. (2023)
  • Author(s): 田中麻理子, 濱田毅, 国田朱子, 長谷川潔, 牛久哲男.
  • Organizer: 第112回日本病理学会総会
• [Presentation] 胸膜肺芽腫の前立腺転移再発と前立腺胎児型横紋筋肉腫との鑑別が問題となったDICER1症候群の一例. (2023)
  • Author(s): 外園晋夫, 田中麻理子, 井上秀太郎, 加藤元博, 牛久哲男.
  • Organizer: 第98回日本病理学会関東支部学術集会
• [Presentation] 癌との鑑別に難渋したタキサン系抗癌剤による十二指腸乳頭部粘膜傷害の1例. (2023)
  • Author(s): 岩原加奈, 田中麻理子, 牛久哲男.
  • Organizer: 第100回日本病理学会関東支部学術集会
• [Book] 十二指腸非乳頭部腺腫・癌の病理診断. 臨牀消化器内科 (2023)
  • Author(s): 名和純一, 田中麻理子, 牛久哲男.
  • Total Pages: 7
  • Publisher: 日本メディカルセンター